O43809 · CPSF5_HUMAN
- ProteinCleavage and polyadenylation specificity factor subunit 5
- GeneNUDT21
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids227 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:14690600, PubMed:15937220, PubMed:17024186, PubMed:17098938, PubMed:29276085, PubMed:8626397, PubMed:9659921).
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:14690600, PubMed:17024186, PubMed:8626397, PubMed:9659921).
Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:17098938, 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:17098938, PubMed:20695905, PubMed:29276085).
NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7 (PubMed:29276085).
Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing (PubMed:14690600, PubMed:15169763, PubMed:17024186, PubMed:20479262, PubMed:22813749, PubMed:8626397).
The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA (PubMed:20479262, PubMed:21295486).
Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function (By similarity).
Binds to chromatin (By similarity).
Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629).
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:14690600, PubMed:17024186, PubMed:8626397, PubMed:9659921).
Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:17098938, 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:17098938, PubMed:20695905, PubMed:29276085).
NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7 (PubMed:29276085).
Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing (PubMed:14690600, PubMed:15169763, PubMed:17024186, PubMed:20479262, PubMed:22813749, PubMed:8626397).
The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA (PubMed:20479262, PubMed:21295486).
Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function (By similarity).
Binds to chromatin (By similarity).
Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 55 | Interaction with RNA | ||||
Sequence: E | ||||||
Site | 63 | Interaction with RNA | ||||
Sequence: R |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCleavage and polyadenylation specificity factor subunit 5
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO43809
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Shuttles between the nucleus and the cytoplasm in a transcription- and XPO1/CRM1-independent manner, most probably in complex with the cleavage factor Im complex (CFIm) (PubMed:19864460).
In punctate subnuclear structures localized adjacent to nuclear speckles, called paraspeckles (PubMed:15169763).
In punctate subnuclear structures localized adjacent to nuclear speckles, called paraspeckles (PubMed:15169763).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 23 | Abolishes acetylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 29 | No effect on acetylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 55 | Reduces affinity for UGUARNA by 88%. | ||||
Sequence: E → A | ||||||
Mutagenesis | 63 | Reduces affinity for UGUARNA by 99%. | ||||
Sequence: R → S | ||||||
Mutagenesis | 81 | Reduces affinity for UGUARNA by 12%. | ||||
Sequence: E → A | ||||||
Mutagenesis | 103 | Reduces affinity for UGUARNA by 99%. | ||||
Sequence: F → A | ||||||
Mutagenesis | 103 | Reduces affinity for UGUARNA by over 90%. | ||||
Sequence: F → W | ||||||
Mutagenesis | 154 | Reduces affinity for UGUARNA by 50%. | ||||
Sequence: E → A | ||||||
Mutagenesis | 158 | Abolishes interaction with CPSF6; when associated with A-160. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 160 | Abolishes interaction with CPSF6; when associated with A-158. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 218 | Reduces interactions with CPSF6 and CPSF7 and decreases mRNA 3'-processing activity. | ||||
Sequence: L → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 80 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Chain | PRO_0000057150 | 2-227 | Cleavage and polyadenylation specificity factor subunit 5 | |||
Sequence: SVVPPNRSQTGWPRGVTQFGNKYIQQTKPLTLERTINLYPLTNYTFGTKEPLYEKDSSVAARFQRMREEFDKIGMRRTVEGVLIVHEHRLPHVLLLQLGTTFFKLPGGELNPGEDEVEGLKRLMTEILGRQDGVLQDWVIDDCIGNWWRPNFEPPQYPYIPAHITKPKEHKKLFLVQLQEKALFAVPKNYKLVAAPLFELYDNAPGYGPIISSLPQLLSRFNFIYN | ||||||
Modified residue | 15 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 23 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 29 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 40 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 56 | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Acetylated mainly by p300/CBP, recruited to the complex by CPSF6. Acetylation decreases interaction with PAPAO. Deacetylated by the class I/II HDACs, HDAC1, HDAC3 and HDAC10, and by the class III HDACs, SIRT1 and SIRT2.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (via N- and C-terminus); binds RNA as homodimer (PubMed:18445629, PubMed:20479262, PubMed:20695905).
Component of the cleavage factor Im (CFIm) complex which is a heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7 (PubMed:14561889, PubMed:20695905, PubMed:21295486, PubMed:23187700, PubMed:8626397, PubMed:9659921).
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).
Interacts with CPSF6 (via the RRM domain); this interaction is direct and enhances binding to RNA (PubMed:14561889, PubMed:15169763, PubMed:17172643, PubMed:19864460, PubMed:29276085).
Interacts with CPSF7 (PubMed:29276085, Ref.30). Interacts with FIP1L1; this interaction occurs in a RNA sequence-specific manner (PubMed:15937220).
Interacts with PABPN1 (PubMed:15169763).
Interacts (via N-terminus) with PAPOLA (via C-terminus); this interaction is direct and diminished by acetylation (PubMed:15169763, PubMed:17172643).
Interacts with SNRNP70 (PubMed:14561889).
Interacts with VIRMA (PubMed:29507755).
Component of the cleavage factor Im (CFIm) complex which is a heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7 (PubMed:14561889, PubMed:20695905, PubMed:21295486, PubMed:23187700, PubMed:8626397, PubMed:9659921).
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).
Interacts with CPSF6 (via the RRM domain); this interaction is direct and enhances binding to RNA (PubMed:14561889, PubMed:15169763, PubMed:17172643, PubMed:19864460, PubMed:29276085).
Interacts with CPSF7 (PubMed:29276085, Ref.30). Interacts with FIP1L1; this interaction occurs in a RNA sequence-specific manner (PubMed:15937220).
Interacts with PABPN1 (PubMed:15169763).
Interacts (via N-terminus) with PAPOLA (via C-terminus); this interaction is direct and diminished by acetylation (PubMed:15169763, PubMed:17172643).
Interacts with SNRNP70 (PubMed:14561889).
Interacts with VIRMA (PubMed:29507755).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-147 | Necessary for RNA-binding | ||||
Sequence: SVVPPNRSQTGWPRGVTQFGNKYIQQTKPLTLERTINLYPLTNYTFGTKEPLYEKDSSVAARFQRMREEFDKIGMRRTVEGVLIVHEHRLPHVLLLQLGTTFFKLPGGELNPGEDEVEGLKRLMTEILGRQDGVLQDWVIDDCIGN | ||||||
Domain | 76-201 | Nudix hydrolase | ||||
Sequence: MRRTVEGVLIVHEHRLPHVLLLQLGTTFFKLPGGELNPGEDEVEGLKRLMTEILGRQDGVLQDWVIDDCIGNWWRPNFEPPQYPYIPAHITKPKEHKKLFLVQLQEKALFAVPKNYKLVAAPLFEL | ||||||
Region | 81-160 | Necessary for interactions with PAPOLA and PABPN1 | ||||
Sequence: EGVLIVHEHRLPHVLLLQLGTTFFKLPGGELNPGEDEVEGLKRLMTEILGRQDGVLQDWVIDDCIGNWWRPNFEPPQYPY | ||||||
Region | 102-104 | Interaction with RNA | ||||
Sequence: TFF | ||||||
Motif | 109-130 | Nudix box | ||||
Sequence: GELNPGEDEVEGLKRLMTEILG |
Sequence similarities
Belongs to the Nudix hydrolase family. CPSF5 subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length227
- Mass (Da)26,227
- Last updated1998-06-01 v1
- ChecksumD204243E57F1CCC5
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 57 | in Ref. 2; CAG33200 | ||||
Sequence: D → G | ||||||
Sequence conflict | 112 | in Ref. 3; CAD97606 | ||||
Sequence: N → D | ||||||
Sequence conflict | 218 | in Ref. 3; CAD97606 | ||||
Sequence: L → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ001810 EMBL· GenBank· DDBJ | CAA05026.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456919 EMBL· GenBank· DDBJ | CAG33200.1 EMBL· GenBank· DDBJ | mRNA | ||
BX537360 EMBL· GenBank· DDBJ | CAD97606.1 EMBL· GenBank· DDBJ | mRNA | ||
AC092140 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC001403 EMBL· GenBank· DDBJ | AAH01403.1 EMBL· GenBank· DDBJ | mRNA |