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CPSF6 cleavage and polyadenylation specific factor 6 [ Homo sapiens (human) ]

Gene ID: 11052, updated on 6-Jan-2019

Summary

Official Symbol
CPSF6provided by HGNC
Official Full Name
cleavage and polyadenylation specific factor 6provided by HGNC
Primary source
HGNC:HGNC:13871
See related
Ensembl:ENSG00000111605 MIM:604979
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
CFIM; CFIM68; CFIM72; HPBRII-4; HPBRII-7
Summary
The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. The cleavage factor complex is composed of four polypeptides. This gene encodes the 68kD subunit. It has a domain organization reminiscent of spliceosomal proteins. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 16.3), lymph node (RPKM 15.0) and 25 other tissues See more
Orthologs

Genomic context

See CPSF6 in Genome Data Viewer
Location:
12q15
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 12 NC_000012.12 (69239537..69274358)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (69633317..69668138)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene carboxypeptidase M Neighboring gene PRELI domain containing 2 pseudogene 1 Neighboring gene uncharacterized LOC107984471 Neighboring gene C1GALT1 pseudogene 1 Neighboring gene microRNA 1279 Neighboring gene lysozyme

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
A genome-wide association study identifies susceptibility loci of silica related pneumoconiosis in Han Chinese.
NHGRI GWA Catalog
Many sequence variants affecting diversity of adult human height.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 incorporates CPSF6 into virions PubMed
Knockdown of CPSF6, TNPO3, or NUP153 through siRNA leads to decreased CA and viral DNA nuclear entry PubMed
HIV-1 CA binds CPSF6 to enhance nuclear entry PubMed

Protein interactions

Protein Gene Interaction Pubs
Rev rev HIV-1 Rev interacting protein, cleavage and polyadenylation specific factor 6, (CPSF6), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with CPSF6 is increased by RRE PubMed
capsid gag HIV-1 CA binds CPSF6; this interaction is inhibited by the inhibitor BI-2 PubMed
gag HIV-1 CA binds CPSF6 to enhance HIV-1 nuclear entry PubMed
gag HIV-1 CA relocalizes RANBP2 (NUP358) into the cytoplasm of infected cells, which requires CPSF6 and KIF5B PubMed
gag HIV-1 CA binds to CPSF6, which is abrogated by mutation A77V in CA and confers a significant viral fitness advantage PubMed
gag HIV-1 CA binds CPSF6; HIV-1 CA mutations S41A, Q67H, V165I and V172I in combination abrogate this interaction PubMed
gag CPSF6 (313-327) F321N mutant impairs to bind to HIV-1 CA monomers and hexamers, and is inactive in the functional Epic assay PubMed
gag CPSF6 binds to the CA hexamer more tightly than the isolated CA NTD or unassembled CA, and the binding of CPSF6 to the hexamer involves energetically significant contacts with both the NTD and CTD in CA PubMed
gag Truncated CPSF6-358 binds HIV-1 core complexes and N74D CA mutant impairs the interaction between CPSF6-358 and CA PubMed
gag HIV-1 inhibition by TNPO3 knockdown and CPSF6-358 is CA-dependent and cytoplasmic localization of CPSF6-358 is required to inhibit HIV-1 PubMed
gag Crystal structure analysis demonstrates that helixes 3, 4, 8, and 9 in HIV-1 CA are involved in its binding to the CPSF6 peptide (residues 313-327) PubMed
gag Five substitutions Q67H, K70R, H87P, T107N, and L111I in HIV-1 CA resistant to PF74 reduce the binding of the host protein CPSF6 to assembled CA complexes in vitro and permit infection of cells expressing the inhibitory protein CPSF6-358 PubMed
gag Endogenously expressed CPSF6 binds and stabilizes in vitro-assembled HIV-1 CA-NC complexes, but the CPSF6-FG284AA mutant loses the ability to bind and stabilize the CA-NC complexes PubMed
gag The C-terminal residues 314-322 of CPSF6-358 contribute to binding with HIV-1 CA and mutations within this region fail to restrict HIV-1 PubMed
gag Residues N57, M66, Q67, K70, N74, and T107 in the N-terminal domain of HIV-1 CA are important for the binding to CPSF6. Mutations on these residues lead to the loss or reduction of dependency on TNPO3 and RanBP2 PubMed
gag HIV-1 CA mutants N74D and P90A fail to bind to CPSF6 and cyclophilins (Nup358 and CypA), respectively, and trigger innate sensors, leading to nuclear translocation of NFkappaB and IRF3, production of type 1 IFN and induction of an antiviral state PubMed
gag HIV-1 CA T107I and N74D substitutions can rescue the CA mutant RKLM by reducing the binding to CPSF6, while the CA S41A substitution resuces RKLM from CPSF6 inhibition without significantly changing the extent of CPSF6 binding PubMed
gag The HIV-1 CA mutant T54A infection is inhibited by CPSF6, but the A106T substitution in CA reduces the association of CPSF6 with CA to resuce the mutant T54A PubMed
gag Cytoplasmic CPSF6 stabilizes the HIV-1 CA core and TNPO3 is required for CPSF6 localization to the nucleus and the HIV-1 permissiveness. However, some studies indicate depletion of TNPO3 does not change the cellular distribution of CPSF6 PubMed
nucleocapsid gag Endogenously expressed CPSF6 binds and stabilizes in vitro-assembled HIV-1 CA-NC complexes, but the CPSF6-FG284AA mutant loses the ability to bind and stabilize the CA-NC complexes PubMed
reverse transcriptase gag-pol Mutational analyses reveal that the residues encoded by exon 6, but not the C-terminal 54 residues in hCPSF6-375, is responsible for inhibition of HIV-1 RT-mediated viral cDNA synthesis PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • FGFR1 mutant receptor activation, organism-specific biosystem (from REACTOME)
    FGFR1 mutant receptor activation, organism-specific biosystemThe FGFR1 gene has been shown to be subject to activating mutations, chromosomal rearrangements and gene amplification leading to a variety of proliferative and developmental disorders depending on w...
  • Signaling by FGFR in disease, organism-specific biosystem (from REACTOME)
    Signaling by FGFR in disease, organism-specific biosystemA number of skeletal and developmental diseases have been shown to arise as a result of mutations in the FGFR1, 2 and 3 genes. These include dwarfism syndromes (achondroplasia, hypochondroplasia and...
  • Signaling by FGFR1 in disease, organism-specific biosystem (from REACTOME)
    Signaling by FGFR1 in disease, organism-specific biosystemThe FGFR1 gene has been shown to be subject to activating mutations, chromosomal rearrangements and gene amplification leading to a variety of proliferative and developmental disorders depending on w...
  • Signaling by cytosolic FGFR1 fusion mutants, organism-specific biosystem (from REACTOME)
    Signaling by cytosolic FGFR1 fusion mutants, organism-specific biosystem8p11 myeloproliferative syndrome (EMS) is an aggressive disorder that is associated with a translocation event at the FGFR1 gene on chromosome 8p11. Typical symptoms upon diagnosis include eosinophi...
  • 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 ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
RNA binding HDA PubMed 
contributes_to RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
exon-exon junction complex binding IDA
Inferred from Direct Assay
more info
PubMed 
mRNA binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ribosomal large subunit binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
mRNA alternative polyadenylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
mRNA processing IDA
Inferred from Direct Assay
more info
PubMed 
messenger ribonucleoprotein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of RNA export from nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
pre-mRNA cleavage required for polyadenylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein heterotetramerization IDA
Inferred from Direct Assay
more info
PubMed 
protein tetramerization IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
interchromatin granule IDA
Inferred from Direct Assay
more info
PubMed 
mRNA cleavage and polyadenylation specificity factor complex IDA
Inferred from Direct Assay
more info
PubMed 
mRNA cleavage factor complex IDA
Inferred from Direct Assay
more info
PubMed 
membrane HDA PubMed 
nuclear speck IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
paraspeckles IDA
Inferred from Direct Assay
more info
PubMed 
perichromatin fibrils IDA
Inferred from Direct Assay
more info
PubMed 
ribonucleoprotein complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
cleavage and polyadenylation specificity factor subunit 6
Names
CPSF 68 kDa subunit
cleavage and polyadenylation specific factor 6, 68kDa
cleavage and polyadenylation specificity factor 68 kDa subunit
cleavage factor Im complex 68 kDa subunit
pre-mRNA cleavage factor I, 68kD subunit
pre-mRNA cleavage factor Im (68kD)
pre-mRNA cleavage factor Im 68 kDa subunit
protein HPBRII-4/7

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_001300947.1NP_001287876.1  cleavage and polyadenylation specificity factor subunit 6 isoform 2

    See identical proteins and their annotated locations for NP_001287876.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) represents the longer transcript and encodes the longer isoform (2).
    Source sequence(s)
    AC020656, AW189370, BC000714, DA365448
    Consensus CDS
    CCDS73494.1
    UniProtKB/Swiss-Prot
    Q16630
    Related
    ENSP00000266679.8, ENST00000266679.8
    Conserved Domains (2) summary
    COG0724
    Location:9152
    RRM; RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis]
    cd12643
    Location:82158
    RRM_CFIm68; RNA recognition motif of pre-mRNA cleavage factor Im 68 kDa subunit (CFIm68 or CPSF6) and similar proteins
  2. NM_007007.3NP_008938.2  cleavage and polyadenylation specificity factor subunit 6 isoform 1

    See identical proteins and their annotated locations for NP_008938.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) lacks an alternate in-frame exon in the central coding region, compared to variant 2. The encoded isoform (1) is shorter than isoform 2.
    Source sequence(s)
    AC020656, AK223568, AW189370, DA365448
    Consensus CDS
    CCDS8988.1
    UniProtKB/Swiss-Prot
    Q16630
    Related
    ENSP00000391774.2, ENST00000435070.6
    Conserved Domains (1) summary
    cd12643
    Location:82158
    RRM_CFIm68; RNA recognition motif of pre-mRNA cleavage factor Im 68 kDa subunit (CFIm68 or CPSF6) and similar proteins

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p12 Primary Assembly

    Range
    69239537..69274358
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005268588.3XP_005268645.1  cleavage and polyadenylation specificity factor subunit 6 isoform X1

    See identical proteins and their annotated locations for XP_005268645.1

    Conserved Domains (2) summary
    COG0724
    Location:9152
    RRM; RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis]
    cd12643
    Location:82158
    RRM_CFIm68; RNA recognition motif of pre-mRNA cleavage factor Im 68 kDa subunit (CFIm68 or CPSF6) and similar proteins
  2. XM_005268590.3XP_005268647.1  cleavage and polyadenylation specificity factor subunit 6 isoform X2

    See identical proteins and their annotated locations for XP_005268647.1

    Conserved Domains (1) summary
    cd12643
    Location:82158
    RRM_CFIm68; RNA recognition motif of pre-mRNA cleavage factor Im 68 kDa subunit (CFIm68 or CPSF6) and similar proteins
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