UniProtKB - Q9QXK7 (CPSF3_MOUSE)
Cleavage and polyadenylation specificity factor subunit 3
Cpsf3
Functioni
Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays 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. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3' endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner. Required for the selective processing of microRNAs (miRNAs) during embryonic stem cell differentiation via its interaction with ISY1 (PubMed:26255770, PubMed:29804889).
Required for entering/progressing through S-phase of the cell cycle (By similarity).
Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (PubMed:26255770).
Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (PubMed:29804889).
By similarity5 PublicationsCofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 71 | Zinc 1By similarity | 1 | |
Metal bindingi | 73 | Zinc 1By similarity | 1 | |
Metal bindingi | 75 | Zinc 2By similarity | 1 | |
Metal bindingi | 76 | Zinc 2By similarity | 1 | |
Metal bindingi | 158 | Zinc 1By similarity | 1 | |
Metal bindingi | 179 | Zinc 1By similarity | 1 | |
Metal bindingi | 179 | Zinc 2By similarity | 1 | |
Active sitei | 396 | Proton donorSequence analysis | 1 | |
Metal bindingi | 418 | Zinc 2By similarity | 1 |
GO - Molecular functioni
- 5'-3' exonuclease activity Source: GO_Central
- 5'-3' exoribonuclease activity Source: UniProtKB
- endoribonuclease activity Source: UniProtKB
- metal ion binding Source: UniProtKB
- RNA binding Source: UniProtKB
GO - Biological processi
- mRNA 3'-end processing by stem-loop binding and cleavage Source: UniProtKB
- mRNA polyadenylation Source: GO_Central
- positive regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
- RNA phosphodiester bond hydrolysis, exonucleolytic Source: UniProtKB
Keywordsi
Molecular function | Endonuclease, Hydrolase, Nuclease, Ribonucleoprotein, RNA-binding |
Biological process | mRNA processing |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-159231, Transport of Mature mRNA Derived from an Intronless Transcript R-MMU-72163, mRNA Splicing - Major Pathway R-MMU-72187, mRNA 3'-end processing R-MMU-73856, RNA Polymerase II Transcription Termination R-MMU-77595, Processing of Intronless Pre-mRNAs |
Names & Taxonomyi
Protein namesi | Recommended name: Cleavage and polyadenylation specificity factor subunit 3 (EC:3.1.27.-1 Publication)Alternative name(s): Cleavage and polyadenylation specificity factor 73 kDa subunit Short name: CPSF 73 kDa subunit Short name: mRNA 3'-end-processing endonuclease CPSF-73 |
Gene namesi | Name:Cpsf3 Synonyms:Cpsf73 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1859328, Cpsf3 |
VEuPathDBi | HostDB:ENSMUSG00000054309 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 75 – 76 | DH → KA: Abolishes cleavage of the 5' autoinhibitory fragment of the long primary miRNA transcript, pri-miR-17-92. 1 Publication | 2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000074401 | 2 – 684 | Cleavage and polyadenylation specificity factor subunit 3Add BLAST | 683 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineBy similarity | 1 | |
Cross-linki | 462 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Cross-linki | 465 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Cross-linki | 545 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Modified residuei | 659 | PhosphoserineCombined sources | 1 | |
Modified residuei | 681 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q9QXK7 |
jPOSTi | Q9QXK7 |
MaxQBi | Q9QXK7 |
PaxDbi | Q9QXK7 |
PeptideAtlasi | Q9QXK7 |
PRIDEi | Q9QXK7 |
ProteomicsDBi | 283939 |
PTM databases
iPTMneti | Q9QXK7 |
PhosphoSitePlusi | Q9QXK7 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000054309, Expressed in floor plate of midbrain and 310 other tissues |
ExpressionAtlasi | Q9QXK7, baseline and differential |
Genevisiblei | Q9QXK7, MM |
Interactioni
Subunit structurei
Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1.
Interacts with CPSF2, CSTF2 and SYMPK.
Interacts with TUT1; the interaction is direct and mediates the recruitment of the CPSF complex on the 3'UTR of pre-mRNAs.
Interacts with WDR33 (By similarity).
Interacts with ZC3H3 (PubMed:16115198).
Interacts with ISY1; this interaction is in an RNA independent manner (PubMed:26255770).
Interacts with the microprocessor complex subunits DGCR8 and DROSHA; this interaction is in an RNA dependent manner (PubMed:26255770).
By similarity2 PublicationsProtein-protein interaction databases
BioGRIDi | 207665, 4 interactors |
STRINGi | 10090.ENSMUSP00000068148 |
Miscellaneous databases
RNActi | Q9QXK7, protein |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1137, Eukaryota |
GeneTreei | ENSGT00940000155699 |
HOGENOMi | CLU_009673_2_3_1 |
InParanoidi | Q9QXK7 |
OMAi | TRSVECE |
OrthoDBi | 218195at2759 |
PhylomeDBi | Q9QXK7 |
TreeFami | TF105643 |
Family and domain databases
Gene3Di | 3.60.15.10, 1 hit |
InterProi | View protein in InterPro IPR022712, Beta_Casp IPR021718, CPSF73-100_C IPR001279, Metallo-B-lactamas IPR036866, RibonucZ/Hydroxyglut_hydro IPR011108, RMMBL |
Pfami | View protein in Pfam PF10996, Beta-Casp, 1 hit PF11718, CPSF73-100_C, 1 hit PF00753, Lactamase_B, 1 hit PF07521, RMMBL, 1 hit |
SMARTi | View protein in SMART SM01027, Beta-Casp, 1 hit SM01098, CPSF73-100_C, 1 hit SM00849, Lactamase_B, 1 hit |
SUPFAMi | SSF56281, SSF56281, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MSAIPAEESD QLLIRPLGAG QEVGRSCIIL EFKGRKIMLD CGIHPGLEGM
60 70 80 90 100
DALPYIDLID PAEIDLLLIS HFHLDHCGAL PWFLQKTSFK GRTFMTHATK
110 120 130 140 150
AIYRWLLSDY VKVSNISADD MLYTETDLEE SMDKIETINF HEVKEVAGIK
160 170 180 190 200
FWCYHAGHVL GAAMFMIEIA GVKLLYTGDF SRQEDRHLMA AEIPNIKPDI
210 220 230 240 250
LIIESTYGTH IHEKREEREA RFCNTVHDIV NRGGRGLIPV FALGRAQELL
260 270 280 290 300
LILDEYWQNH PELHDIPIYY ASSLAKKCMA VYQTYVNAMN DKIRKQININ
310 320 330 340 350
NPFVFKHISN LKSMDHFDDI GPSVVMASPG MIQNGLSREL FESWCTDKRN
360 370 380 390 400
GVIIAGYCVE GTLAKHIMSE PEEITTMSGQ KLPLKMSVDY ISFSAHTDYQ
410 420 430 440 450
QTSEFIRALK PPHVILVHGE QNEMARLKAA LIREYEDNDE VHIEVHNPRN
460 470 480 490 500
TEAVTLNFRG EKLAKVMGFL ADKKPEQGQR VSGILVKRNF NYHILSPCDL
510 520 530 540 550
SNYTDLAMST VKQTQAIPYT GPFYLLYYQL QKLTGDVEEL EIQEKPALKV
560 570 580 590 600
FKSITVVQEP GMVVLEWLAN PSNDMYADTV TTVILEVQSN PKIRKGAVQK
610 620 630 640 650
VSKKLEMHVY SKRLEVMLQD IFGEDCVSVK DDSVLSVTVD GKTANINLET
660 670 680
RAVECEEGSE DDESLREMVE LAAQRLYEAL TPVH
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1Y7VLY3 | A0A1Y7VLY3_MOUSE | Cleavage and polyadenylation-specif... | Cpsf3 | 512 | Annotation score: | ||
A0A1Y7VJ97 | A0A1Y7VJ97_MOUSE | Cleavage and polyadenylation-specif... | Cpsf3 | 247 | Annotation score: | ||
A0A1Y7VIZ9 | A0A1Y7VIZ9_MOUSE | Cleavage and polyadenylation-specif... | Cpsf3 | 241 | Annotation score: | ||
A0A1Y7VJU9 | A0A1Y7VJU9_MOUSE | Cleavage and polyadenylation-specif... | Cpsf3 | 156 | Annotation score: | ||
A0A1Y7VNI9 | A0A1Y7VNI9_MOUSE | Cleavage and polyadenylation-specif... | Cpsf3 | 28 | Annotation score: | ||
A0A1Y7VJV9 | A0A1Y7VJV9_MOUSE | Cleavage and polyadenylation-specif... | Cpsf3 | 15 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 223 – 224 | CN → WH in AAF19420 (Ref. 1) Curated | 2 | |
Sequence conflicti | 541 | E → D in AAF19420 (Ref. 1) Curated | 1 | |
Sequence conflicti | 564 – 565 | VL → GS in AAF19420 (Ref. 1) Curated | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF203969 mRNA Translation: AAF19420.1 BC023297 mRNA Translation: AAH23297.1 |
CCDSi | CCDS25834.1 |
RefSeqi | NP_061283.2, NM_018813.3 |
Genome annotation databases
Ensembli | ENSMUST00000067284; ENSMUSP00000068148; ENSMUSG00000054309 |
GeneIDi | 54451 |
KEGGi | mmu:54451 |
UCSCi | uc007ndp.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF203969 mRNA Translation: AAF19420.1 BC023297 mRNA Translation: AAH23297.1 |
CCDSi | CCDS25834.1 |
RefSeqi | NP_061283.2, NM_018813.3 |
3D structure databases
SMRi | Q9QXK7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 207665, 4 interactors |
STRINGi | 10090.ENSMUSP00000068148 |
PTM databases
iPTMneti | Q9QXK7 |
PhosphoSitePlusi | Q9QXK7 |
Proteomic databases
EPDi | Q9QXK7 |
jPOSTi | Q9QXK7 |
MaxQBi | Q9QXK7 |
PaxDbi | Q9QXK7 |
PeptideAtlasi | Q9QXK7 |
PRIDEi | Q9QXK7 |
ProteomicsDBi | 283939 |
Protocols and materials databases
Antibodypediai | 12409, 223 antibodies from 27 providers |
DNASUi | 54451 |
Genome annotation databases
Ensembli | ENSMUST00000067284; ENSMUSP00000068148; ENSMUSG00000054309 |
GeneIDi | 54451 |
KEGGi | mmu:54451 |
UCSCi | uc007ndp.2, mouse |
Organism-specific databases
CTDi | 51692 |
MGIi | MGI:1859328, Cpsf3 |
VEuPathDBi | HostDB:ENSMUSG00000054309 |
Phylogenomic databases
eggNOGi | KOG1137, Eukaryota |
GeneTreei | ENSGT00940000155699 |
HOGENOMi | CLU_009673_2_3_1 |
InParanoidi | Q9QXK7 |
OMAi | TRSVECE |
OrthoDBi | 218195at2759 |
PhylomeDBi | Q9QXK7 |
TreeFami | TF105643 |
Enzyme and pathway databases
Reactomei | R-MMU-159231, Transport of Mature mRNA Derived from an Intronless Transcript R-MMU-72163, mRNA Splicing - Major Pathway R-MMU-72187, mRNA 3'-end processing R-MMU-73856, RNA Polymerase II Transcription Termination R-MMU-77595, Processing of Intronless Pre-mRNAs |
Miscellaneous databases
BioGRID-ORCSi | 54451, 24 hits in 66 CRISPR screens |
ChiTaRSi | Cpsf3, mouse |
PROi | PR:Q9QXK7 |
RNActi | Q9QXK7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000054309, Expressed in floor plate of midbrain and 310 other tissues |
ExpressionAtlasi | Q9QXK7, baseline and differential |
Genevisiblei | Q9QXK7, MM |
Family and domain databases
Gene3Di | 3.60.15.10, 1 hit |
InterProi | View protein in InterPro IPR022712, Beta_Casp IPR021718, CPSF73-100_C IPR001279, Metallo-B-lactamas IPR036866, RibonucZ/Hydroxyglut_hydro IPR011108, RMMBL |
Pfami | View protein in Pfam PF10996, Beta-Casp, 1 hit PF11718, CPSF73-100_C, 1 hit PF00753, Lactamase_B, 1 hit PF07521, RMMBL, 1 hit |
SMARTi | View protein in SMART SM01027, Beta-Casp, 1 hit SM01098, CPSF73-100_C, 1 hit SM00849, Lactamase_B, 1 hit |
SUPFAMi | SSF56281, SSF56281, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CPSF3_MOUSE | |
Accessioni | Q9QXK7Primary (citable) accession number: Q9QXK7 Secondary accession number(s): Q8CIM0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 18, 2001 |
Last sequence update: | July 27, 2011 | |
Last modified: | February 23, 2022 | |
This is version 142 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families