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    CPSF4 cleavage and polyadenylation specific factor 4 [ Homo sapiens (human) ]

    Gene ID: 10898, updated on 7-Apr-2024

    Summary

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    Official Symbol
    CPSF4provided by HGNC
    Official Full Name
    cleavage and polyadenylation specific factor 4provided by HGNC
    Primary source
    HGNC:HGNC:2327
    See related
    Ensembl:ENSG00000160917 MIM:603052; AllianceGenome:HGNC:2327
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NAR; NEB1; NEB-1; CPSF30
    Summary
    Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector domain. The NS1 effector domain functionally interacts with the cellular 30 kDa subunit of cleavage and polyadenylation specific factor 4, an essential component of the 3' end processing machinery of cellular pre-mRNAs. In influenza virus-infected cells, the NS1 protein is physically associated with cleavage and polyadenylation specific factor 4, 30kD subunit. Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cleavage and polyadenylation of host pre-mRNAs. Thus the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs. Multiple alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 7.2), lymph node (RPKM 4.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    7q22.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (99438943..99457373)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (100677844..100696279)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (99036566..99054996)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA U13 Neighboring gene BUD31 homolog Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18409 Neighboring gene ATP5MF-PTCD1 readthrough Neighboring gene pentatricopeptide repeat domain 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:99020619-99021120 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:99027477-99028073 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:99032915-99033062 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:99034189-99034714 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26315 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18410 Neighboring gene SAP domain containing ribonucleoprotein pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:99049670-99050230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:99053345-99054147 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:99058948-99059448 Neighboring gene ATP synthase membrane subunit f Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:99062959-99063576 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:99063577-99064192 Neighboring gene tRNA-Trp (anticodon CCA) 5-1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer. Song Y, et al. Med Oncol, 2022 Dec 26. PMID 36567417
    2. CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma. Wang X, et al. Oncogene, 2021 Jun. PMID 34103682
    3. Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma. Zhang M, et al. J Oral Maxillofac Surg, 2021 May. PMID 33535057
    4. Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe-2S cluster. Shimberg GD, et al. Proc Natl Acad Sci U S A, 2016 Apr 26. PMID 27071088, Free PMC Article
    5. Upregulation of cleavage and polyadenylation specific factor 4 in lung adenocarcinoma and its critical role for cancer cell survival and proliferation. Chen W, et al. PLoS One, 2013. PMID 24358221, Free PMC Article

    See all (86) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro.
      Title: Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro.
    2. CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer.
      Title: CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer.
    3. CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4.
      Title: CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4.
    4. CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma.
      Title: CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma.
    5. Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma.
      Title: Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma.
    6. MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4; results suggest that the miR-4458-CPSF4-COX-2-hTERT axis might serve as a potential target for the treatment of breast cancer patients
      Title: MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4.
    7. The authors define the molecular architecture of the core human CPSF complex comprising CPSF160, WDR33, CPSF30 and Fip1 and identify specific domains involved in inter-subunit interactions. Together, these results shed light on the function of CPSF in mediating polyA signal-dependent RNA cleavage and polyadenylation.
      Title: Structural insights into the assembly and polyA signal recognition mechanism of the human CPSF complex.
    8. Residues F103 and M106 within the NS1-CPSF4 binding region are important for viral replication.
      Title: Residues F103 and M106 within the influenza A virus NS1 CPSF4-binding region regulate interferon-stimulated gene translation initiation.
    9. Cleavage and polyadenylation specific factor 4 targets NF-kappaB/cyclooxygenase-2 signaling to promote the growth and survival of non-small cell lung carcinoma cells.
      Title: Cleavage and polyadenylation specific factor 4 targets NF-κB/cyclooxygenase-2 signaling to promote lung cancer growth and progression.
    10. These findings support a role for iron in some zinc-finger proteins. Using electrophoretic mobility shift assays and fluorescence anisotropy, we report that CPSF30 selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF30/RNA binding.
      Title: Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe-2S cluster.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in mRNA processing IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    part_of mRNA cleavage and polyadenylation specificity factor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of mRNA cleavage and polyadenylation specificity factor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    cleavage and polyadenylation specificity factor subunit 4
    Names
    CPSF 30 kDa subunit
    NS1 effector domain-binding protein 1
    cleavage and polyadenylation specific factor 4, 30kDa
    cleavage and polyadenylation specificity factor 30 kDa subunit
    no arches homolog
    no arches-like zinc finger protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001081559.3 → NP_001075028.1  cleavage and polyadenylation specificity factor subunit 4 isoform 2

      See identical proteins and their annotated locations for NP_001075028.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AA040394, AI076832, BM757197, BM787372, BQ052009
      Consensus CDS
      CCDS47652.1
      UniProtKB/TrEMBL
      C9JEV9
      Related
      ENSP00000395311.2, ENST00000436336.6
      Conserved Domains (2) summary
      COG5084
      Location:25 → 176
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:201 → 233
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    2. NM_001318160.2 → NP_001305089.1  cleavage and polyadenylation specificity factor subunit 4 isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      BC003101, BC050738, BM757197
      UniProtKB/TrEMBL
      C9JEV9
      Related
      ENSP00000396060.1, ENST00000451876.5
      Conserved Domains (2) summary
      COG5084
      Location:25 → 176
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:200 → 232
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    3. NM_001318161.2 → NP_001305090.1  cleavage and polyadenylation specificity factor subunit 4 isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) has multiple differences in the coding region, one of which results in a frameshift, compared to variant 1. The encoded isoform (4) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      BC003101, BE388179, BM757197
      UniProtKB/TrEMBL
      H7C016
      Related
      ENSP00000392584.1, ENST00000452047.1
      Conserved Domains (2) summary
      smart00356
      Location:63 → 88
      ZnF_C3H1; zinc finger
      COG5084
      Location:25 → 159
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]

    4. NM_001318162.2 → NP_001305091.1  cleavage and polyadenylation specificity factor subunit 4 isoform 5

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) contains an alternate 5'-terminal exon, uses an alternate splice site in the 3' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (5) is shorter than isoform 1.
      Source sequence(s)
      AK301745, BC003101
      Consensus CDS
      CCDS83205.1
      UniProtKB/TrEMBL
      B7Z7B0
      Related
      ENSP00000402224.1, ENST00000441580.5
      Conserved Domains (2) summary
      COG5084
      Location:2 → 123
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:148 → 180
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    5. NM_006693.4 → NP_006684.1  cleavage and polyadenylation specificity factor subunit 4 isoform 1

      See identical proteins and their annotated locations for NP_006684.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AA040394, BM757197, BQ641871, CX754488, U79569
      Consensus CDS
      CCDS5664.1
      UniProtKB/Swiss-Prot
      D6W5S8, O95639, Q6FGE6, Q86TF8, Q9BTW6
      Related
      ENSP00000292476.5, ENST00000292476.10
      Conserved Domains (2) summary
      COG5084
      Location:25 → 211
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:226 → 258
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      99438943..99457373
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011515755.4 → XP_011514057.1  cleavage and polyadenylation specificity factor subunit 4 isoform X1

      Conserved Domains (2) summary
      COG5084
      Location:25 → 161
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:231 → 263
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    2. XM_011515756.4 → XP_011514058.1  cleavage and polyadenylation specificity factor subunit 4 isoform X2

      UniProtKB/TrEMBL
      C9JEV9
      Conserved Domains (2) summary
      COG5084
      Location:25 → 161
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:206 → 238
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    3. XM_011515757.3 → XP_011514059.1  cleavage and polyadenylation specificity factor subunit 4 isoform X3

      UniProtKB/TrEMBL
      C9JEV9
      Conserved Domains (2) summary
      COG5084
      Location:25 → 161
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:205 → 237
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    4. XM_047419827.1 → XP_047275783.1  cleavage and polyadenylation specificity factor subunit 4 isoform X7

    5. XM_047419824.1 → XP_047275780.1  cleavage and polyadenylation specificity factor subunit 4 isoform X4

    6. XM_047419825.1 → XP_047275781.1  cleavage and polyadenylation specificity factor subunit 4 isoform X5

    7. XM_047419826.1 → XP_047275782.1  cleavage and polyadenylation specificity factor subunit 4 isoform X6

    8. XM_017011703.3 → XP_016867192.1  cleavage and polyadenylation specificity factor subunit 4 isoform X4

      Conserved Domains (2) summary
      COG5084
      Location:2 → 108
      YTH1; Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only]
      COG5222
      Location:178 → 210
      COG5222; Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only]

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      100677844..100696279
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054357141.1 → XP_054213116.1  cleavage and polyadenylation specificity factor subunit 4 isoform X1

    2. XM_054357142.1 → XP_054213117.1  cleavage and polyadenylation specificity factor subunit 4 isoform X2

    3. XM_054357143.1 → XP_054213118.1  cleavage and polyadenylation specificity factor subunit 4 isoform X3

    4. XM_054357148.1 → XP_054213123.1  cleavage and polyadenylation specificity factor subunit 4 isoform X7

    5. XM_054357144.1 → XP_054213119.1  cleavage and polyadenylation specificity factor subunit 4 isoform X4

    6. XM_054357146.1 → XP_054213121.1  cleavage and polyadenylation specificity factor subunit 4 isoform X5

    7. XM_054357147.1 → XP_054213122.1  cleavage and polyadenylation specificity factor subunit 4 isoform X6

    8. XM_054357145.1 → XP_054213120.1  cleavage and polyadenylation specificity factor subunit 4 isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95639.1 GenPept UniProtKB/Swiss-Prot:O95639

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