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   07-APR-2021, entry version 139.
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 play 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 the biogenesis of all
CC       miRNAs from the pri-miR-17-92 primary transcript except miR-92a
CC       (PubMed:26255770). Only required for the biogenesis of miR-290 and miR-
CC       96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts,
CC       respectively (PubMed:29804889). {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   SMR; Q9QXK7; -.
DR   BioGRID; 207665; 4.
DR   IntAct; Q9QXK7; 1.
DR   MINT; Q9QXK7; -.
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; 222 antibodies.
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   eggNOG; KOG1137; Eukaryota.
DR   GeneTree; ENSGT00940000155699; -.
DR   HOGENOM; CLU_009673_2_3_1; -.
DR   InParanoid; Q9QXK7; -.
DR   OrthoDB; 218195at2759; -.
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; 21 hits in 53 CRISPR screens.
DR   ChiTaRS; Cpsf3; mouse.
DR   PRO; PR:Q9QXK7; -.
DR   Proteomes; UP000000589; Chromosome 12.
DR   RNAct; Q9QXK7; protein.
DR   Bgee; ENSMUSG00000054309; Expressed in midbrain and 303 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; IDA:UniProtKB.
DR   GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
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   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   METAL           71
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           73
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           75
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           76
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           158
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           179
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           179
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UKF6"
FT   METAL           418
FT                   /note="Zinc 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
//