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    CPSF3 cleavage and polyadenylation specific factor 3, 73kDa [ Homo sapiens ]

    Gene ID: 51692, updated on 11-May-2012
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    Summary

    Official Symbol
    CPSF3provided by HGNC
    Official Full Name
    cleavage and polyadenylation specific factor 3, 73kDaprovided by HGNC
    Primary source
    HGNC:2326
    See related
    Ensembl:ENSG00000119203; HPRD:05825; MIM:606029; Vega:OTTHUMG00000090415
    Gene type
    protein coding
    RefSeq status
    PROVISIONAL
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CPSF; YSH1; CPSF73; CPSF-73
    Summary
    Most eukaryotic mRNA precursors (pre-mRNAs) undergo extensive maturational processing, including cleavage and polyadenylation at the 3-prime end. CPSF3 encodes the 73-kD subunit of the cleavage and polyadenylation specificity factor (CPSF) and is the pre-mRNA 3-prime-end-processing endonuclease (Mandel et al., 2006 [PubMed 17128255]).[supplied by OMIM, Jul 2010]
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    Genomic context

    Location :
    2p25.1
    Sequence :
    Chromosome: 2; NC_000002.11 (9563868..9613227)
    See CPSF3 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 Neighboring gene integrin beta 1 binding protein 1 Neighboring gene uncharacterized LOC100506357 Neighboring gene isoamyl acetate-hydrolyzing esterase 1 homolog (S. cerevisiae) Neighboring gene ADAM metallopeptidase domain 17

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Global identification of modular cullin-RING ligase substrates. Emanuele MJ, et al. Cell, 2011 Oct 14. PMID 21963094.
    2. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    3. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.
    4. Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1. Rowbotham SP, et al. Mol Cell, 2011 May 6. PMID 21549307.
    5. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Danielsen JM, et al. Mol Cell Proteomics, 2011 Mar. PMID 21139048.

    See all (31) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. The data support a model where Star-PAP binds to the pre-mRNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs.
      Title: The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA.
    2. The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors.
      Title: The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors.
    3. CSR1 appears to induce cell death through a novel mechanism by hijacking a critical RNA processing enzyme CPSF3.
      Title: CSR1 induces cell death through inactivation of CPSF3.
    4. Degradation of the downstream cleavage product (DCP) does not depend on the Xrn2 5' exonuclease, suggesting that CPSF-73 degrades the DCP both in vitro and in vivo.
      Title: Studies of the 5' exonuclease and endonuclease activities of CPSF-73 in histone pre-mRNA processing.
    5. Conserved residues in CPSF-73 and CPSF2 are required for assembly of the endonuclease activity that cleaves histone pre-mRNAs.
      Title: Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation.
    6. this study identifies CPSF-73 as an important regulatory protein that represses the basal transcriptional activity of the HIV-1 LTR promoter
      Title: The 73 kDa subunit of the CPSF complex binds to the HIV-1 LTR promoter and functions as a negative regulatory factor that is inhibited by the HIV-1 Tat protein.
    7. up-regulated by HIV-1 TAT protein; this could represent a novel mechanism by which HIV increases mRNA processing, causing an increase in both cell and viral gene expression.
      Title: Human immunodeficiency virus type 1 Tat increases the expression of cleavage and polyadenylation specificity factor 73-kilodalton subunit modulating cellular and viral expression.
    8. crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions and a sulphate that might mimic the phosphate group of the substrate; CPSF-73 is the pre-mRNA 3'-end-processing endonuclease
      Title: Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
    Submit: New GeneRIF Correction
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat specifically increases the expression of the cleavage and polyadenylation specificity factor 73-kDa subunit (CPSF3), and this upregulation is an important regulatory step for both viral and cellular gene expression PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q9UKF6 Q92989 CLP1    HPRD  PubMed  
    Q9UKF6 P51003 PAPOLA    HPRD  PubMed  
    Q9UKF6 P24928 POLR2A    HPRD  PubMed  
    Q9UKF6 P61981 YWHAG    HPRD  PubMed  
    BioGRID:119680 BioGRID:122724 CDC73    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:119680 BioGRID:115912 RRAGA    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Co-fractionation 
    BioGRID:119680 BioGRID:121244 SMARCAD1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:119680 BioGRID:112771 TBP    BioGRID  PubMed Affinity Capture-RNA 
    BioGRID:119680 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:119680 BioGRID:119707 WWOX    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    • Homologs of the CPSF3 gene: The CPSF3 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, , S.pombe, , N.crassa, A.thaliana, and rice.
    • Map Viewer (Mouse, Rat)

    Pathways from BioSystems

    • Cleavage of Growing Transcript in the Termination Region, organism-specific biosystem (from REACTOME)
      Cleavage of Growing Transcript in the Termination Region, organism-specific biosystemThis section includes the cleavage of both polyadenylated and non-polyadenylated transcripts. In the former case polyadenylation has to precede transcript cleavage, while in the latter case there is ...
    • Gene Expression, organism-specific biosystem (from REACTOME)
      Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
    • Processing of Capped Intron-Containing Pre-mRNA, organism-specific biosystem (from REACTOME)
      Processing of Capped Intron-Containing Pre-mRNA, organism-specific biosystemCo-transcriptional pre-mRNA splicing is not obligatory. Pre-mRNA splicing begins co-transcriptionally and often continues post-transcriptionally. Human genes contain an average of nine introns per ge...
    • Processing of Capped Intronless Pre-mRNA, organism-specific biosystem (from REACTOME)
      Processing of Capped Intronless Pre-mRNA, organism-specific biosystemCo-transcriptional pre-mRNA splicing is not obligatory. Pre-mRNA splicing begins co-transcriptionally and often continues post-transcriptionally. Human genes contain an average of nine introns per ge...
    • Processing of Intronless Pre-mRNAs, organism-specific biosystem (from REACTOME)
      Processing of Intronless Pre-mRNAs, organism-specific biosystemThe 3' ends of eukaryotic mRNAs are generated by posttranscriptional processing of an extended primary transcript. For almost all RNAs, 3' processing consists of two steps: The mRNA is first cleaved ...
    • RNA Polymerase II Transcription, organism-specific biosystem (from REACTOME)
      RNA Polymerase II Transcription, organism-specific biosystem
      RNA Polymerase II Transcription
    • RNA Polymerase II Transcription Termination, organism-specific biosystem (from REACTOME)
      RNA Polymerase II Transcription Termination, organism-specific biosystemThe detailed annotation of this section will be completed in the next release.
    • Transport of Mature Transcript to Cytoplasm, organism-specific biosystem (from REACTOME)
      Transport of Mature Transcript to Cytoplasm, organism-specific biosystemTransport of mRNA through the Nuclear Pore Complex (NPC) is a dynamic process involving distinct machinery and receptor subsets. The separation of the two compartments and the regulation of this tran...
    • Transport of Mature mRNA Derived from an Intronless Transcript, organism-specific biosystem (from REACTOME)
      Transport of Mature mRNA Derived from an Intronless Transcript, organism-specific biosystemTransport of mRNA from the nucleus to the cytoplasm, where it is translated into protein, is highly selective and closely coupled to correct RNA processing.
    • Transport of Mature mRNAs Derived from Intronless Transcripts, organism-specific biosystem (from REACTOME)
      Transport of Mature mRNAs Derived from Intronless Transcripts, organism-specific biosystemTransport of mature mRNAs derived from intronless transcripts require some of the same protein complexes as mRNAs derived from intron containing complexes, including TAP and Aly/Ref. However a number...
    • mRNA 3'-end processing, organism-specific biosystem (from REACTOME)
      mRNA 3'-end processing, organism-specific biosystemThe 3' ends of eukaryotic mRNAs are generated by posttranscriptional processing of an extended primary transcript. For almost all RNAs, 3'-end processing consists of two steps: (i) the mRNA is first ...
    • mRNA Splicing, organism-specific biosystem (from REACTOME)
      mRNA Splicing, organism-specific biosystemThe process in which excision of introns from the primary transcript of messenger RNA (mRNA) is followed by ligation of the two exon termini exposed by removal of each intron, is called mRNA splicing...
    • mRNA Splicing - Major Pathway, organism-specific biosystem (from REACTOME)
      mRNA Splicing - Major Pathway, organism-specific biosystemThe splicing of pre-mRNA occurs within a large, very dynamic complex, designated the 'spliceosome'. The 50-60S spliceosomes are estimated to be 40-60 nm in diameter, and have molecular weights in the...
    • mRNA processing, organism-specific biosystem (from WikiPathways)
      mRNA processing, organism-specific biosystemThis process describes the conversion of precursor messenger RNA into mature messenger RNA (mRNA). The pre-mRNA molecule undergoes three main modifications. These modifications are 5' capping, 3' po...
    • mRNA surveillance pathway, organism-specific biosystem (from KEGG)
      mRNA surveillance pathway, organism-specific biosystemThe mRNA surveillance pathway is a quality control mechanism that detects and degrades abnormal mRNAs. These pathways include nonsense-mediated mRNA decay (NMD), nonstop mRNA decay (NSD), and no-go ...
    • mRNA surveillance pathway, conserved biosystem (from KEGG)
      mRNA surveillance pathway, conserved biosystemThe mRNA surveillance pathway is a quality control mechanism that detects and degrades abnormal mRNAs. These pathways include nonsense-mediated mRNA decay (NMD), nonstop mRNA decay (NSD), and no-go ...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    5'-3' exonuclease activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    RNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    endoribonuclease activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    RNA splicing TAS
    Traceable Author Statement
    more info
    		  
    gene expression TAS
    Traceable Author Statement
    more info
    		  
    histone mRNA 3'-end processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    mRNA 3'-end processing TAS
    Traceable Author Statement
    more info
    		  
    mRNA cleavage TAS
    Traceable Author Statement
    more info
    		 PubMed 
    mRNA export from nucleus TAS
    Traceable Author Statement
    more info
    		  
    mRNA polyadenylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    mRNA processing TAS
    Traceable Author Statement
    more info
    		  
    nuclear mRNA splicing, via spliceosome TAS
    Traceable Author Statement
    more info
    		  
    termination of RNA polymerase II transcription TAS
    Traceable Author Statement
    more info
    		  
    transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    mRNA cleavage and polyadenylation specificity factor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    ribonucleoprotein complex IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    cleavage and polyadenylation specificity factor subunit 3
    Names
    cleavage and polyadenylation specificity factor subunit 3
    CPSF 73 kDa subunit
    mRNA 3'-end-processing endonuclease CPSF-73
    cleavage and polyadenylation specificity factor 3
    cleavage and polyadenylation specificity factor 73 kDa subunit
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    NCBI Reference Sequences (RefSeq)

    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_016207.2 → NP_057291.1  cleavage and polyadenylation specificity factor subunit 3

      Status: PROVISIONAL

      Source sequence(s)
      BC020211
      Consensus CDS
      CCDS1664.1
      UniProtKB/Swiss-Prot
      Q9UKF6
      Related
      ENSP00000238112, OTTHUMP00000115483, ENST00000238112, OTTHUMT00000206843
      Conserved Domains (5) summary
      COG1236
      Location:12 – 456
      Blast Score: 999
      YSH1; Predicted exonuclease of the beta-lactamase fold involved in RNA processing [Translation, ribosomal structure and biogenesis]
      cl13209
      Location:477 – 683
      Blast Score: 634
      CPSF73-100_C; Pre-mRNA 3'-end-processing endonuclease polyadenylation factor C-term
      pfam07521
      Location:380 – 422
      Blast Score: 135
      RMMBL; RNA-metabolising metallo-beta-lactamase
      cl00446
      Location:26 – 195
      Blast Score: 185
      Lactamase_B; Metallo-beta-lactamase superfamily
      cl12567
      Location:246 – 367
      Blast Score: 395
      Beta-Casp; Beta-Casp domain

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p5 Primary Assembly

      Range
      9563868..9613227
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      9409351..9458750
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC080162.7 AAY14858.1
    genomic CH471053.2 EAX00989.1
      EAX00990.1
    mRNA AF017269.1 AAB70268.1
    mRNA AF171877.1 AAF00224.1
    mRNA AK025440.1 None
    mRNA AK223487.1 BAD97207.1
    mRNA AK298918.1 BAG61024.1
    mRNA BC011654.2 AAH11654.1
    mRNA BC014106.1 None
    mRNA BC020211.1 AAH20211.1
    mRNA BC030988.1 AAH30988.1
    mRNA BC043432.2 None
    mRNA EF036508.1 ABO65094.1
    other-genetic EU176402.1 ABW03853.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q05BZ5 GenPept UniProtKB/TrEMBL:Q05BZ5
    Q53F02 GenPept UniProtKB/TrEMBL:Q53F02
    Q9UKF6.1 GenPept UniProtKB/Swiss-Prot:Q9UKF6
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

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