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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
Location 7q22.1      Physical location : 99.036.562 - 99.054.994
Synonym name
  • cleavage-polyadenylation specificity factor, 30kD
  • NS1 effector domain-binding protein 1
  • no arches homolog
  • no arches-like zinc finger protein
  • Synonym symbol(s) NAR, NEB1, CPSF30, CPSF-30, NEB-1
    DNA
    TYPE functioning gene
    STRUCTURE 18.47 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    DKFZp761L1417 7q22.1 hypothetical protein DKFZp761L1417 TRRAP 7q21.3-q22.1 transformation/transcription domain-associated protein SMURF1 7q21.1-q31.1 transformation/transcription domain-associated protein LOC389539 7 similar to importin alpha 1b ARPC1A 7q22.1-q31.33 actin related protein 2/3 complex, subunit 1A, 41kDa ARPC1B 7q22.1-q31.33 actin related protein 2/3 complex, subunit 1B, 41kDa PDAP1 7q11.21 PDGFA associated protein 1 G10 7q11.21 PDGFA associated protein 1 CPSF4 7q22.1 cleavage and polyadenylation specific factor 4, 30kDa KIAA0632 7q22.1 cleavage and polyadenylation specific factor 4, 30kDa ATP5J2 7q21.3-q22 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit f, isoform 2 LOC285989 7q22.1 hypothetical protein LOC285989 ZNF394 7q22.1 zinc finger protein 394 ZFP95 7q22 zinc finger protein 95 homolog (mouse) DKFZp727G131 7q22.1 hypothetical protein DKFZp727G131 VIK 7q22.1 vav-1 interacting Kruppel-like protein ZNF498 7q22.1 zinc finger protein 498 CYP3A5 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 CYP3A5P1 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 pseudogene 1 CYP3A7 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 7 CYP3A5P2 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 pseudogene 2 CYP3A4 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 4 CYP3A43 7q21.1 cytochrome P450, family 3, subfamily A, polypeptide 43 TRIM4 7q22-q31.1 tripartite motif-containing 4 AZGP1 7q22.1 alpha-2-glycoprotein 1, zinc LOC392078 7 hypothetical gene supported by BC022382 ZNF36 7q21.3-q22.1 zinc finger protein 36 (KOX 18)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1823 - 269 - 1997 9224719
    8 - 1775 - 244 - 1997 9224719
    8 - 1772 - 243 - 1997 9224719
    7 - 1681 - 262 - 1997 9224719
    8 - 1750 - 191 - 1997 9224719
    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