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FLASH GENE
Symbol CPSF4 contributors: mct - updated : 23-03-2020
HGNC name cleavage and polyadenylation specific factor 4, 30kDa
HGNC id 2327
EXPRESSION
Type ubiquitous
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestivesalivary gland   highly
Reproductivefemale systemuteruscervix highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a RNA-binding zinc finger protein, with five Cys3His domains (annotated as "zinc-finger" domains, that is a critical determinant of specific AAUAAA motif recognition
  • mono polymer complex
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation
  • CPSF4 and its homologues are likely the actual nucleases that cleave pre-mRNA in the process of polyadenylation
  • plays a key role in mRNA polyadenylation and mRNA 3' ends maturation
  • plays a critical role in regulating lung cancer cell proliferation and survival
  • CPSF4 and WDR33 directly contact AAUAAA
  • key protein involved in pre-mRNA processing
  • CPSF1 functions as an essential scaffold and preorganizes CPSF4 and WDR33 for high-affinity binding to AAUAAA
  • selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF4/RNA binding
  • crucial tumorigenic factor in lung cancer development
  • both CPSF4 and WDR33 are required for high-affinity binding of the AAUAAA polyadenylation signal (PAS) RNA, while these two proteins alone and their binary complexes with CPSF1 have much lower affinity for the RNA
  • CELLULAR PROCESS nucleotide, transcription, maturation
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    text polyadenylation
    PATHWAY
    metabolism
    signaling
  • role of the CPSF4/PTGS2 signaling pathway in the regulation of lung cancer growth and progression
  • a component
  • complexing with CPSF1, 2, 3 poly (A) ribonuclease (PARN) and CSTF3 (cleavage stimulation factor 3)
  • a core CPSF complex comprising CPSF1, WDR33, CPSF4 and FIP1L1 is sufficient for AAUAAA motif recognition, necessary for 3' polyadenylation, a key step in eukaryotic mRNA biogenesis
  • INTERACTION
    DNA
    RNA binding to the AAUAA motif of the pre mRNA, upstream the cleavage site
    small molecule
    protein
  • associate with some other CPSF subunits
  • NS1A proteins of human influenza A viruses bind CPSF4, a cellular factor required for the processing of cellular pre-mRNAs, thereby inhibiting the production of all cellular mRNAs, including beta interferon mRNA(pMID: 17522219)
  • CPSF4 plays a critical role in the regulation of TERT expression and lung tumorigenesis and may be a new prognosis factor in lung adenocarcinomas
  • CREBBP regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathways 8)
  • CPSF4 bind to PTGS2 promoter sequences directly and activate the transcription of PTGS2
  • CPSF4 facilitated colorectal tumorigenesis and development partially through transcriptionally regulating TERT expression by cooperating with NFKB1 and co-anchoring at TERT promoter -321 to -234 fragment
  • cell & other
    REGULATION
    inhibited by influenza virus NS1 protein
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in human colon cancer cells and tissues
    tumoral     --over  
    in lung adenocarcinoma cell lines and tumor tissue (pMID: 24358221)
    tumoral     --over  
    of CPSF4 and PTGS2 proteins predicted poor prognosis of patients with lung cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may be a potential prognostic biomarker for lung adenocarcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    targeting CPSF4-TERT axis may represent a promising therapeutic strategy in colon cancer treatment
    cancerlung 
    potential therapeutic target for lung adenocarcinoma
    ANIMAL & CELL MODELS