Human Gene CPSF4 (uc003uqj.3)
  Description: Homo sapiens cleavage and polyadenylation specific factor 4, 30kDa (CPSF4), transcript variant 1, mRNA.
RefSeq Summary (NM_006693): 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].
Transcript (Including UTRs)
   Position: hg19 chr7:99,036,563-99,054,996 Size: 18,434 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg19 chr7:99,036,706-99,054,123 Size: 17,418 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:99,036,563-99,054,996)mRNA (may differ from genome)Protein (269 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CPSF4_HUMAN
DESCRIPTION: RecName: Full=Cleavage and polyadenylation specificity factor subunit 4; AltName: Full=Cleavage and polyadenylation specificity factor 30 kDa subunit; Short=CPSF 30 kDa subunit; AltName: Full=NS1 effector domain-binding protein 1; Short=Neb-1; AltName: Full=No arches homolog;
FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).
SUBUNIT: Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with FIP1L1. Association with influenza A virus NS1 blocks processing of pre-mRNAs, thereby preventing nuclear export of host cell mRNAs.
SUBCELLULAR LOCATION: Nucleus.
SIMILARITY: Belongs to the CPSF4/YTH1 family.
SIMILARITY: Contains 5 C3H1-type zinc fingers.
SIMILARITY: Contains 1 CCHC-type zinc finger.
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/cpsf4/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CPSF4
CDC HuGE Published Literature: CPSF4

-  MalaCards Disease Associations
  MalaCards Gene Search: CPSF4
Diseases sorted by gene-association score: influenza (14), benign essential hypertension (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 24.33 RPKM in Testis
Total median expression: 569.01 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -75.10143-0.525 Picture PostScript Text
3' UTR -355.84873-0.408 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000571 - Znf_CCCH
IPR001878 - Znf_CCHC

Pfam Domains:
PF00098 - Zinc knuckle
PF00642 - Zinc finger C-x8-C-x5-C-x3-H type (and similar)
PF14608 - RNA-binding, Nab2-type zinc finger
PF15663 - Zinc-finger containing family

SCOP Domains:
90229 - CCCH zinc finger

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2D9N - NMR MuPIT 2RHK - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O95639
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details  Gene Details  
Gene Sorter  Gene Sorter  
  EnsemblFlyBase  
  Protein SequenceProtein Sequence  
  AlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003676 nucleic acid binding
GO:0003723 RNA binding
GO:0004521 endoribonuclease activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0046872 metal ion binding

Biological Process:
GO:0000398 mRNA splicing, via spliceosome
GO:0006369 termination of RNA polymerase II transcription
GO:0006378 mRNA polyadenylation
GO:0006397 mRNA processing
GO:0006406 mRNA export from nucleus
GO:0016032 viral process
GO:0031124 mRNA 3'-end processing
GO:0046778 modification by virus of host mRNA processing
GO:0090502 RNA phosphodiester bond hydrolysis, endonucleolytic
GO:0098789 pre-mRNA cleavage required for polyadenylation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005847 mRNA cleavage and polyadenylation specificity factor complex
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  JC506674 - Sequence 42 from Patent EP2733220.
JC737786 - Sequence 42 from Patent WO2014075939.
JC506688 - Sequence 56 from Patent EP2733220.
JC737800 - Sequence 56 from Patent WO2014075939.
BC050738 - Homo sapiens cleavage and polyadenylation specific factor 4, 30kDa, mRNA (cDNA clone MGC:60384 IMAGE:6199123), complete cds.
BC003101 - Homo sapiens cleavage and polyadenylation specific factor 4, 30kDa, mRNA (cDNA clone MGC:1870 IMAGE:3356071), complete cds.
U79569 - Human no arches (nar) mRNA, complete cds.
AB529148 - Synthetic construct DNA, clone: pF1KB5204, Homo sapiens CPSF4 gene for cleavage and polyadenylation specific factor 4, 30kDa, without stop codon, in Flexi system.
CU690790 - Synthetic construct Homo sapiens gateway clone IMAGE:100021318 5' read CPSF4 mRNA.
HQ448622 - Synthetic construct Homo sapiens clone IMAGE:100072061; CCSB011823_01 cleavage and polyadenylation specific factor 4, 30kDa (CPSF4) gene, encodes complete protein.
KJ893157 - Synthetic construct Homo sapiens clone ccsbBroadEn_02551 CPSF4 gene, encodes complete protein.
KJ902171 - Synthetic construct Homo sapiens clone ccsbBroadEn_11565 CPSF4 gene, encodes complete protein.
CR542161 - Homo sapiens full open reading frame cDNA clone RZPDo834C0424D for gene CPSF4, cleavage and polyadenylation specific factor 4, 30kDa; complete cds, without stopcodon.
AK301745 - Homo sapiens cDNA FLJ52791 complete cds, highly similar to Cleavage and polyadenylation specificityfactor 30 kDa subunit.
JD210384 - Sequence 191408 from Patent EP1572962.
JD229891 - Sequence 210915 from Patent EP1572962.
JD103059 - Sequence 84083 from Patent EP1572962.
JD247440 - Sequence 228464 from Patent EP1572962.
JD227459 - Sequence 208483 from Patent EP1572962.
JD399129 - Sequence 380153 from Patent EP1572962.
JD131979 - Sequence 113003 from Patent EP1572962.
JD343279 - Sequence 324303 from Patent EP1572962.
JD384328 - Sequence 365352 from Patent EP1572962.
JD209414 - Sequence 190438 from Patent EP1572962.
JD519409 - Sequence 500433 from Patent EP1572962.
JD392950 - Sequence 373974 from Patent EP1572962.
JD230573 - Sequence 211597 from Patent EP1572962.
JD515562 - Sequence 496586 from Patent EP1572962.
JD178515 - Sequence 159539 from Patent EP1572962.
JD224246 - Sequence 205270 from Patent EP1572962.
JD332662 - Sequence 313686 from Patent EP1572962.
JD051245 - Sequence 32269 from Patent EP1572962.
JD161399 - Sequence 142423 from Patent EP1572962.
JD150929 - Sequence 131953 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_cpsfPathway - Polyadenylation of mRNA

Reactome (by CSHL, EBI, and GO)

Protein O95639 (Reactome details) participates in the following event(s):

R-HSA-168859 Binding of NS1 to cleavage and host polyadenylation specificity factor (CPSF)
R-HSA-72231 Cleavage and Polyadenylation
R-HSA-77589 Recognition of AAUAAA sequence by CPSF
R-HSA-72185 mRNA polyadenylation
R-HSA-77594 Docking of the Mature intronless derived transcript derived mRNA, TAP and Aly/Ref at the NPC
R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex
R-HSA-72180 Cleavage of mRNA at the 3'-end
R-HSA-77590 Recruitment of CstF to the CPSF Bound Pre-mRNA
R-HSA-77592 Cleavage of Intronless Pre-mRNA at 3'-end
R-HSA-77593 Cleavage and polyadenylation of Intronless Pre-mRNA
R-HSA-5696813 TSEN complex cleaves the intron from pre-tRNA
R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage
R-HSA-72139 Formation of the active Spliceosomal C (B*) complex
R-HSA-8849157 TREX complex binds spliced, capped mRNA:CBC:EJC cotranscriptionally
R-HSA-156661 Formation of Exon Junction Complex
R-HSA-77591 Binding of Cleavage factors and Poly(A)Polymerase to the CstF:CPSF:Pre-mRNA Complex
R-HSA-168315 Inhibition of Host mRNA Processing and RNA Silencing
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-77595 Processing of Intronless Pre-mRNAs
R-HSA-72187 mRNA 3'-end processing
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-168276 NS1 Mediated Effects on Host Pathways
R-HSA-109688 Cleavage of Growing Transcript in the Termination Region
R-HSA-72172 mRNA Splicing
R-HSA-75067 Processing of Capped Intronless Pre-mRNA
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts
R-HSA-6784531 tRNA processing in the nucleus
R-HSA-168253 Host Interactions with Influenza Factors
R-HSA-73856 RNA Polymerase II Transcription Termination
R-HSA-8953854 Metabolism of RNA
R-HSA-72202 Transport of Mature Transcript to Cytoplasm
R-HSA-72306 tRNA processing
R-HSA-168254 Influenza Infection
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-5663205 Infectious disease
R-HSA-74160 Gene expression (Transcription)
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: CPSF30, CPSF4_HUMAN, D6W5S8, NAR, NEB1, NM_006693, NP_006684, O95639, Q6FGE6, Q86TF8, Q9BTW6
UCSC ID: uc003uqj.3
RefSeq Accession: NM_006693
Protein: O95639 (aka CPSF4_HUMAN or CPSD_HUMAN)
CCDS: CCDS5664.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_006693.2
exon count: 8CDS single in 3' UTR: no RNA size: 1829
ORF size: 810CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1820.00frame shift in genome: no % Coverage: 99.84
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.