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FLASH GENE
Symbol WDR77 contributors: mct/npt/pgu - updated : 21-10-2016
HGNC name WD repeat domain 77
HGNC id 29652
Location 1p13.2      Physical location : 111.982.512 - 111.991.830
Synonym name
  • methylosome protein 50
  • MEP50 protein
  • androgen receptor cofactor p44
  • Synonym symbol(s) MGC2722, HKMT1069, MEP50, RP11-552M11.3, Nbla10071, RP11-552M11 3, p44, p44/Mep50
    DNA
    TYPE functioning gene
    STRUCTURE 9.42 kb     10 Exon(s)
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • promoter contains bona fide response elements for E2F and GATA transcriptional factors, and is transactivated by E2F1, E2F3, GATA1 and GATA6, but suppressed by E2F6, GATA1 and GATA3 in prostate cancer PC3 cells
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2522 - 340 - 2014 25277535
    8 - 2336 - 278 - 2014 25277535
    10 - 2528 36.6 342 - 2014 25277535
    10 - 2564 - 354 - 2014 25277535
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Lymphoid/Immunetonsils   highly
    Reproductivemale systemprostate  highly Homo sapiensFetal
    Respiratorylung     Homo sapiensFetal
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five WD repeats
  • mono polymer homomer , dimer , tetramer
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • nuclear and cytoplasmic form have distinct and opposing functions in the regulation of prostate cancer cell proliferation (cytoplasmic enhancing cell proliferation and nuclear inhibiting this proliferation)
  • localizes in the cytoplasm of prostate epithelial cells at the early stage of prostate development when cells are proliferating, and its nuclear translocation is associated with cellular and functional differentiation in adult prostate tissue
  • expressed in the cytoplasm of germ cells of the fetal testis
  • expressed predominantly as nuclear proteins in fetal Leydig cells and human adult nonneoplastic testes, including germ cells and Leydig cells
  • PRMT5 and WDR77 were evenly distributed between cytoplasm and nucleus
  • basic FUNCTION
  • functioning to mediate the interaction of multiple substrates with the methylosome
  • involved in Sm protein rearrangements or pre-assembly required for snRNP biogenesis
  • required for proper expression of AR-target genes to maintain the differentiation of prostate epithelial cells, and its translocation from the nucleus into the cytoplasm in prostate cancer cells results in excessive prostate EC proliferation
  • distinct functions of the nuclear and the WDR77/PRMT5 complexes in the developing fetal testis and in the oncogenesis of testicular tumors
  • plays a critical role in the proliferation and differentiation of prostate epithelial cells
  • novel role for WDR77 in the control of astrocyte activation through CDKN1A and NFKB1 signaling
  • nuclear WDR77 is required for cell differentiation and prostate- specific protein secretion, but cytoplasmic protein is essential for proliferation of prostate epithelial cells
  • drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells
  • its expression causes the non-sensitivity of proliferating cells to TGFB1 signaling, thereby contributing to cellular proliferation during lung tumorigenesis
  • WDR77 can transform cells independent of AR and ESR, and PRMT5 has partial contribution to that process
  • likely WDR77 and PRMT5 simultaneously engage the protein substrate, orienting its targeted arginine to the catalytic site
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the methylosome
  • PRMT5/WDR77 complex for pluripotency, may occur in conjunction with the leukemia inhibitory factor (LIF)/STAT3 pathway
  • PRMT5/WDR77-dependent methylation is an epigenetic mechanism that assists in silencing of IVL expression, and PRKCD signaling activates gene expression by directly activating transcription and by suppressing PRMT5/WDR77-dependent arginine dimethylation of promoter-associated histones
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to JBP1 and to a subset of Sm proteins
  • coactivator of androgen receptor (AR), with distinct growth suppression and promotion function in gender specific endocrine organs and their malignancies
  • PRKG1 is a novel regulator of AR-mediated transcription by enhancing AR cofactor WDR77 function, which provide a novel mechanism for the growth regulation of prostate cancer cells by the androgen signaling
  • down-regulates the expression of the TGFB1 ligand and its receptor, thereby leading to a cellular non-response to TGFB1 signaling
  • is a coactivator for androgen receptor (AR) and estrogen receptor (ESR), and transforms cells in the presence of androgen or estrogen
  • PRMT5 interacts with a cofactor, WDR77(MEP50), and symmetrically dimethylates arginine eight of histone 3 (H3R8me2s) and arginine three of histone 4 (H4R3me2s) to silence gene expression
  • cell & other
    REGULATION
    Other is regulated during erythroid and lung development and lung tumorigenesis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    altered expression is associated with androgen-independent prostate cancer
    tumoral     --other  
    seminoma and Leydig tumor cells showed a marked decrease in nuclear expression of WDR77 and PRMT5 with a concomitant marked increase in cytoplasmic expression of these proteins
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deletion of the Wdr77 gene caused premature death with dramatic astrogliosis in mouse brain