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CPSF6 (Q16630) - Overview - Molecular Target Synopsis

Protein


CPSF6, Cleavage and polyadenylation specificity factor subunit 6
UniProt Q16630

Also Known as CPSF6_HUMAN, CPSF6, CFIM68

Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:9659921, PubMed:8626397, PubMed:14690600, PubMed:29276085). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:9659921, PubMed:8626397, PubMed:14690600). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery (PubMed:15169763, PubMed:29276085, PubMed:21295486). Plays a role in mRNA export (PubMed:19864460). Component of the cleavage factor Im (CFIm) complex which is an heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or an heterodimer of CPSF6 and CPSF7 (PubMed:9659921, PubMed:8626397, PubMed:14561889, PubMed:20695905, PubMed:23187700). The cleavage factor Im (CFIm) complex associates with the CPSF and CSTF complexes to promote the assembly of the core mRNA 3'-processing machinery (PubMed:29276085). Associates with the exon junction complex (EJC) (PubMed:19864460). Associates with the 80S ribosome particle (PubMed:19864460). Interacts (via the RRM domain) with NUDT21/CPSF5; this interaction is direct and enhances binding to RNA (PubMed:14561889, PubMed:15169763, PubMed:19864460, PubMed:29276085, PubMed:21295486). Interacts (via Arg/Ser-rich domain) with FIP1L1 (preferentially via unphosphorylated form and Arg/Glu/Asp-rich domain); this interaction mediates, at least in part, the interaction between the CFIm and CPSF complexes and may be inhibited by CPSF6 hyper-phosphorylation (PubMed:29276085). Interacts (via N-terminus) with NXF1; this interaction is direct (PubMed:19864460). Interacts with SRSF3 (PubMed:15169763). Interacts with SRSF7 (PubMed:15169763). Interacts with SNRNP70 (PubMed:14561889). Interacts with TRA2B/SFRS10 (PubMed:15169763). Interacts with UPF1 (PubMed:19864460). Interacts with UPF3B (PubMed:19864460). Interacts with VIRMA (PubMed:29507755).

6GX9
8 RESIDUE FRAGMENT OF
CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR SUBUNIT 6
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF THE TNPO3 - CPSF6 RSLD COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for CPSF6

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CPSF6 is active in the following subcellular-locations: cytoplasm, nucleoplasm, nucleus, nucleus speckle.
GO terms: CPSF6 is active in the following subcellular-locations: cytoplasm, interchromatin granule, membrane, mRNA cleavage and polyadenylation specificity factor complex, mRNA cleavage factor complex, nuclear speck, nucleoplasm, nucleus, paraspeckles, perichromatin fibrils, ribonucleoprotein complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CPSF6 has gain in 8 cell-lines, loss in 2 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, K_562, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: TK, SK-N-DZ, Jurkat, Clone E6-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, HSMM

(see details)

3D Structures


For CPSF6 there are:
10 structures (46 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis