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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
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Genomic context

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See CPSF4 in Genome Data Viewer
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

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

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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