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FLASH GENE
Symbol CDC73 contributors: mct/pgu - updated : 02-05-2012
HGNC name cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae)
HGNC id 16783
DNA
TYPE anonymous DNA segment
STRUCTURE 132.86 kb     17 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 5942 - 531 - 2009 19136632
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
endocrinebraindiencephalonpituitary  
Endocrinepancreas    
 parathyroid   highly
 thyroid   highly
Nervousnervespinal nervesciatic  
Reproductivefemale systembreastmammary gland highly
Respiratorylung    
Urinarykidney    
Visualeyeanterior segmentiris  
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly
Epithelialsecretoryglandularendocrine 
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, fetal, pregnancy
Text placenta, stem cells, eye
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • five NLSs (three bipartite (BP) and two monopartite (MP))
  • C-domain, important for PAF1 complex occupancy on transcribed chromatin, probably constituting a protein interaction surface that functions with RTF1 in coupling the PAF1 complex to the RNA polymerase II elongation machinery
  • the functional bipartite nuclear ocalization signal (NLS) at AAs 136-139 (nucleotides 373-417), KRAADEVLAEAKKPR, that is evolutionarily conserved and critical for the nuclear localization
  • C-terminal arm of this bipartite NLS plays the primary role in nuclear localization
  • mono polymer complex
    HOMOLOGY
    interspecies ortholog to Drosophila Hrpt2
    homolog to murine Cdc73 (100.0pc)
    homolog to rattus Hrpt2 (100.0pc)
    Homologene
    FAMILY CDC73 family
    CATEGORY
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • nucleocytoplasmic protein with functions consistent with its postulated role as a tumor suppressor protein
  • may be involved in transcriptional and post-transcriptional control pathways
  • may be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression
  • mediating the transcriptional outputs of beta-catenin/Armadillo
  • in the context of the PAF1 complex, mediates repression of the MYC proto-oncogene through both transcriptional and posttranscriptional mechanisms
  • nuclear protein that possesses anti-proliferative properties
  • is required for nuclear transduction of the Wnt/Wg signal and depends on the recruitment of Pygopus proteins
  • playing a role as an inhibitor of cell cycle progression
  • may have a role as an important regulator of transcription
  • has a critical role in cell growth
  • having a proapoptotic activity likely important in its role as a tumor suppressor and a functional role for the NLS is required in this activity
  • potentially facilitates association of 3prime mRNA processing factors with actively-transcribed chromatin and support the importance of links between tumor suppression and mRNA maturation
  • implicated in apoptosis and growth arrest
  • may exert both transcriptional and, through CPEB1, translational control over a subset of target genes and that loss of parafibromin (and CPEB1) function may promote tumorigenesis in part by conferring resistance to nutritional stress
  • required for the maintenance of histone 2B monoubiquitination
  • RTF1, CDC73, and LEO1 have all been shown to play a role in recruitment of PAF1C to chromatin at active genes
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • complexing with LEO1, PAF1, CTR9
  • accessory factor for RNA polymerase II as part of the PAF1 complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with human orthologs of yeast Paf1 complex components, including PAF1, LEO1, and CTR9, that are involved in transcription elongation and 3' end processing
  • interact with a histone methyltransferase complex that methylates histone H3 and inhibit proliferation
  • loss of either RTF1 or CDC73 results in the detachment of the PAF1 complex from Pol II and the chromatin form of actively transcribed genes
  • associates with the cleavage and polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CSTF3) complexes that are required for the maturation of mRNA 3 prime ends in the cell nucleus
  • BTK directly interacts with a nuclear component of Wnt-beta-catenin signaling, CDC73
  • tumor suppressor that inhibits CCND1 and MYC by recruiting SUV39H1 histone methyltransferase
  • RNF20 and RNF40 are binding partners of CDC73
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HRPT2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation LOH    
    in hyperparathyroidism-jaw tumor(HPT-JT)
    tumoral somatic mutation      
    in sporadic parathyroid carcinoma
    tumoral germinal mutation      
    in sporadic parathyroid carcinoma
    tumoral       loss of function
    in parathyroid and jaw fibroma
    tumoral       loss of function
    critically facilitates malignant transformation
    tumoral   LOH    
    in clear cell, papillary, chromophobe renal cell carcinomas, oncocytomas and Wilms tumors
    tumoral     --low  
    is involved in the pathogenesis of parathyroid, breast, and gastric carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS