CPSF3_MOUSE
ID CPSF3_MOUSE Reviewed; 684 AA.
AC Q9QXK7; Q8CIM0;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Cleavage and polyadenylation specificity factor subunit 3;
DE EC=3.1.27.- {ECO:0000269|PubMed:18955505};
DE AltName: Full=Cleavage and polyadenylation specificity factor 73 kDa subunit;
DE Short=CPSF 73 kDa subunit;
DE Short=mRNA 3'-end-processing endonuclease CPSF-73;
GN Name=Cpsf3; Synonyms=Cpsf73;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Wang H., Chen W., Yu S., Xie L.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=16213211; DOI=10.1016/j.cell.2005.08.002;
RA Dominski Z., Yang X.-C., Marzluff W.F.;
RT "The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA
RT processing.";
RL Cell 123:37-48(2005).
RN [4]
RP INTERACTION WITH ZC3H3.
RX PubMed=16115198; DOI=10.1111/j.1365-2443.2005.00887.x;
RA Collart C., Remacle J.E., Barabino S., van Grunsven L.A., Nelles L.,
RA Schellens A., Van de Putte T., Pype S., Huylebroeck D., Verschueren K.;
RT "Smicl is a novel Smad interacting protein and cleavage and polyadenylation
RT specificity factor associated protein.";
RL Genes Cells 10:897-906(2005).
RN [5]
RP FUNCTION, RNA-BINDING, AND CATALYTIC ACTIVITY.
RX PubMed=18955505; DOI=10.1128/mcb.00776-08;
RA Yang X.-C., Sullivan K.D., Marzluff W.F., Dominski Z.;
RT "Studies of the 5' exonuclease and endonuclease activities of CPSF-73 in
RT histone pre-mRNA processing.";
RL Mol. Cell. Biol. 29:31-42(2009).
RN [6]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=19470752; DOI=10.1128/mcb.00296-09;
RA Yang X.-C., Torres M.P., Marzluff W.F., Dominski Z.;
RT "Three proteins of the U7-specific Sm ring function as the molecular ruler
RT to determine the site of 3'-end processing in mammalian histone pre-mRNA.";
RL Mol. Cell. Biol. 29:4045-4056(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-659, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, INTERACTION WITH DGCR8; DROSHA AND ISY1, AND MUTAGENESIS OF
RP 75-ASP-HIS-76.
RX PubMed=26255770; DOI=10.1016/j.cell.2015.07.008;
RA Du P., Wang L., Sliz P., Gregory R.I.;
RT "A biogenesis step upstream of microprocessor controls miR-17~92
RT expression.";
RL Cell 162:885-899(2015).
RN [9]
RP FUNCTION.
RX PubMed=29804889; DOI=10.1016/j.stem.2018.04.021;
RA Du P., Pirouz M., Choi J., Huebner A.J., Clement K., Meissner A.,
RA Hochedlinger K., Gregory R.I.;
RT "An intermediate pluripotent state controlled by microRNAs is required for
RT the naive-to-primed stem cell transition.";
RL Cell Stem Cell 22:851-864(2018).
CC -!- FUNCTION: Component of the cleavage and polyadenylation specificity
CC factor (CPSF) complex that plays a key role in pre-mRNA 3'-end
CC formation, recognizing the AAUAAA signal sequence and interacting with
CC poly(A) polymerase and other factors to bring about cleavage and
CC poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-
CC end-processing endonuclease. Also involved in the histone 3'-end pre-
CC mRNA processing. U7 snRNP-dependent protein that induces both the 3'
CC endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to
CC 3' exonuclease for degrading the subsequent downstream cleavage product
CC (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3'
CC sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the
CC upstream fragment containing the stem loop (SL) and 5' phosphate on the
CC downstream cleavage product (DCP) starting with CU nucleotides. The U7-
CC dependent 5' to 3' exonuclease activity is processive and degrades the
CC DCP RNA substrate even after complete removal of the U7-binding site.
CC Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and
CC the cleaved DCP RNA substrate in a U7 snRNP dependent manner. Required
CC for the selective processing of microRNAs (miRNAs) during embryonic
CC stem cell differentiation via its interaction with ISY1
CC (PubMed:26255770, PubMed:29804889). Required for entering/progressing
CC through S-phase of the cell cycle (By similarity). Required for the
CC biogenesis of all miRNAs from the pri-miR-17-92 primary transcript
CC except miR-92a (PubMed:26255770). Only required for the biogenesis of
CC miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary
CC transcripts, respectively (PubMed:29804889).
CC {ECO:0000250|UniProtKB:Q9UKF6, ECO:0000269|PubMed:16213211,
CC ECO:0000269|PubMed:18955505, ECO:0000269|PubMed:19470752,
CC ECO:0000269|PubMed:26255770, ECO:0000269|PubMed:29804889}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9UKF6};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q9UKF6};
CC -!- SUBUNIT: Component of the cleavage and polyadenylation specificity
CC factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and
CC FIP1L1. Interacts with CPSF2, CSTF2 and SYMPK. Interacts with TUT1; the
CC interaction is direct and mediates the recruitment of the CPSF complex
CC on the 3'UTR of pre-mRNAs. Interacts with WDR33 (By similarity).
CC Interacts with ZC3H3 (PubMed:16115198). Interacts with ISY1; this
CC interaction is in an RNA independent manner (PubMed:26255770).
CC Interacts with the microprocessor complex subunits DGCR8 and DROSHA;
CC this interaction is in an RNA dependent manner (PubMed:26255770).
CC {ECO:0000250|UniProtKB:Q9UKF6, ECO:0000269|PubMed:16115198,
CC ECO:0000269|PubMed:26255770}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UKF6}.
CC -!- PTM: Sumoylated on Lys-462, Lys-465 and Lys-545, preferentially by
CC SUMO3. {ECO:0000250|UniProtKB:Q9UKF6}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. RNA-
CC metabolizing metallo-beta-lactamase-like family. CPSF3 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF203969; AAF19420.1; -; mRNA.
DR EMBL; BC023297; AAH23297.1; -; mRNA.
DR CCDS; CCDS25834.1; -.
DR RefSeq; NP_061283.2; NM_018813.3.
DR AlphaFoldDB; Q9QXK7; -.
DR SMR; Q9QXK7; -.
DR BioGRID; 207665; 4.
DR STRING; 10090.ENSMUSP00000068148; -.
DR iPTMnet; Q9QXK7; -.
DR PhosphoSitePlus; Q9QXK7; -.
DR EPD; Q9QXK7; -.
DR jPOST; Q9QXK7; -.
DR MaxQB; Q9QXK7; -.
DR PaxDb; Q9QXK7; -.
DR PeptideAtlas; Q9QXK7; -.
DR PRIDE; Q9QXK7; -.
DR ProteomicsDB; 283939; -.
DR Antibodypedia; 12409; 231 antibodies from 27 providers.
DR DNASU; 54451; -.
DR Ensembl; ENSMUST00000067284; ENSMUSP00000068148; ENSMUSG00000054309.
DR GeneID; 54451; -.
DR KEGG; mmu:54451; -.
DR UCSC; uc007ndp.2; mouse.
DR CTD; 51692; -.
DR MGI; MGI:1859328; Cpsf3.
DR VEuPathDB; HostDB:ENSMUSG00000054309; -.
DR eggNOG; KOG1137; Eukaryota.
DR GeneTree; ENSGT00940000155699; -.
DR HOGENOM; CLU_009673_2_3_1; -.
DR InParanoid; Q9QXK7; -.
DR OMA; TRSVECE; -.
DR OrthoDB; 218195at2759; -.
DR PhylomeDB; Q9QXK7; -.
DR TreeFam; TF105643; -.
DR Reactome; R-MMU-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-MMU-72187; mRNA 3'-end processing.
DR Reactome; R-MMU-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-MMU-77595; Processing of Intronless Pre-mRNAs.
DR BioGRID-ORCS; 54451; 29 hits in 77 CRISPR screens.
DR ChiTaRS; Cpsf3; mouse.
DR PRO; PR:Q9QXK7; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9QXK7; protein.
DR Bgee; ENSMUSG00000054309; Expressed in floor plate of midbrain and 269 other tissues.
DR ExpressionAtlas; Q9QXK7; baseline and differential.
DR Genevisible; Q9QXK7; MM.
DR GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IDA:MGI.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IBA:GO_Central.
DR GO; GO:0004534; F:5'-3' exoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0031124; P:mRNA 3'-end processing; ISO:MGI.
DR GO; GO:0006398; P:mRNA 3'-end processing by stem-loop binding and cleavage; IDA:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; IBA:GO_Central.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0090503; P:RNA phosphodiester bond hydrolysis, exonucleolytic; IDA:UniProtKB.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR022712; Beta_Casp.
DR InterPro; IPR021718; CPSF73-100_C.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR011108; RMMBL.
DR Pfam; PF10996; Beta-Casp; 1.
DR Pfam; PF11718; CPSF73-100_C; 1.
DR Pfam; PF00753; Lactamase_B; 1.
DR Pfam; PF07521; RMMBL; 1.
DR SMART; SM01027; Beta-Casp; 1.
DR SMART; SM01098; CPSF73-100_C; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW Acetylation; Endonuclease; Hydrolase; Isopeptide bond; Metal-binding;
KW mRNA processing; Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW Ribonucleoprotein; RNA-binding; Ubl conjugation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT CHAIN 2..684
FT /note="Cleavage and polyadenylation specificity factor
FT subunit 3"
FT /id="PRO_0000074401"
FT ACT_SITE 396
FT /note="Proton donor"
FT /evidence="ECO:0000255"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 73
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 681
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT CROSSLNK 462
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT CROSSLNK 465
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT CROSSLNK 545
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT MUTAGEN 75..76
FT /note="DH->KA: Abolishes cleavage of the 5' autoinhibitory
FT fragment of the long primary miRNA transcript, pri-miR-17-
FT 92."
FT /evidence="ECO:0000269|PubMed:26255770"
FT CONFLICT 223..224
FT /note="CN -> WH (in Ref. 1; AAF19420)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="E -> D (in Ref. 1; AAF19420)"
FT /evidence="ECO:0000305"
FT CONFLICT 564..565
FT /note="VL -> GS (in Ref. 1; AAF19420)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 684 AA; 77505 MW; 043D09F54284B423 CRC64;
MSAIPAEESD QLLIRPLGAG QEVGRSCIIL EFKGRKIMLD CGIHPGLEGM DALPYIDLID
PAEIDLLLIS HFHLDHCGAL PWFLQKTSFK GRTFMTHATK AIYRWLLSDY VKVSNISADD
MLYTETDLEE SMDKIETINF HEVKEVAGIK FWCYHAGHVL GAAMFMIEIA GVKLLYTGDF
SRQEDRHLMA AEIPNIKPDI LIIESTYGTH IHEKREEREA RFCNTVHDIV NRGGRGLIPV
FALGRAQELL LILDEYWQNH PELHDIPIYY ASSLAKKCMA VYQTYVNAMN DKIRKQININ
NPFVFKHISN LKSMDHFDDI GPSVVMASPG MIQNGLSREL FESWCTDKRN GVIIAGYCVE
GTLAKHIMSE PEEITTMSGQ KLPLKMSVDY ISFSAHTDYQ QTSEFIRALK PPHVILVHGE
QNEMARLKAA LIREYEDNDE VHIEVHNPRN TEAVTLNFRG EKLAKVMGFL ADKKPEQGQR
VSGILVKRNF NYHILSPCDL SNYTDLAMST VKQTQAIPYT GPFYLLYYQL QKLTGDVEEL
EIQEKPALKV FKSITVVQEP GMVVLEWLAN PSNDMYADTV TTVILEVQSN PKIRKGAVQK
VSKKLEMHVY SKRLEVMLQD IFGEDCVSVK DDSVLSVTVD GKTANINLET RAVECEEGSE
DDESLREMVE LAAQRLYEAL TPVH
