ID CPSF5_MOUSE Reviewed; 227 AA.
AC Q9CQF3; Q3UJK1;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 27-MAR-2024, entry version 166.
DE RecName: Full=Cleavage and polyadenylation specificity factor subunit 5 {ECO:0000250|UniProtKB:O43809};
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 21;
DE Short=Nudix motif 21;
DE AltName: Full=Nudix hydrolase 21 {ECO:0000305};
GN Name=Nudt21 {ECO:0000312|MGI:MGI:1915469};
GN Synonyms=Cpsf5 {ECO:0000250|UniProtKB:O43809};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and DBA/2J;
RC TISSUE=Embryo, Embryonic head, Embryonic liver, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Embryonic brain, and Mammary tumor;
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 INTERACTION WITH PAPOLA, AND DOMAIN.
RX PubMed=11716503; DOI=10.1006/bbrc.2001.5992;
RA Kim H., Lee Y.;
RT "Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage
RT factor I.";
RL Biochem. Biophys. Res. Commun. 289:513-518(2001).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP CHROMATIN BINDING.
RX PubMed=18032416; DOI=10.1095/biolreprod.107.064774;
RA Sartini B.L., Wang H., Wang W., Millette C.F., Kilpatrick D.L.;
RT "Pre-messenger RNA cleavage factor I (CFIm): potential role in alternative
RT polyadenylation during spermatogenesis.";
RL Biol. Reprod. 78:472-482(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-23, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-15, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [8]
RP FUNCTION.
RX PubMed=29249356; DOI=10.1016/j.cell.2017.11.023;
RA Brumbaugh J., Di Stefano B., Wang X., Borkent M., Forouzmand E.,
RA Clowers K.J., Ji F., Schwarz B.A., Kalocsay M., Elledge S.J., Chen Y.,
RA Sadreyev R.I., Gygi S.P., Hu G., Shi Y., Hochedlinger K.;
RT "Nudt21 controls cell fate by connecting alternative polyadenylation to
RT chromatin signaling.";
RL Cell 172:106-120(2018).
CC -!- FUNCTION: Component of the cleavage factor Im (CFIm) complex that
CC functions as an activator of the pre-mRNA 3'-end cleavage and
CC polyadenylation processing required for the maturation of pre-mRNA into
CC functional mRNAs. CFIm contributes to the recruitment of multiprotein
CC complexes on specific sequences on the pre-mRNA 3'-end, so called
CC cleavage and polyadenylation signals (pA signals). Most pre-mRNAs
CC contain multiple pA signals, resulting in alternative cleavage and
CC polyadenylation (APA) producing mRNAs with variable 3'-end formation.
CC The CFIm complex acts as a key regulator of cleavage and
CC polyadenylation site choice during APA through its binding to 5'-UGUA-
CC 3' elements localized in the 3'-untranslated region (UTR) for a huge
CC number of pre-mRNAs. NUDT21/CPSF5 activates indirectly the mRNA 3'-
CC processing machinery by recruiting CPSF6 and/or CPSF7. Binds to 5'-
CC UGUA-3' elements localized upstream of pA signals that act as enhancers
CC of pre-mRNA 3'-end processing. The homodimer mediates simultaneous
CC sequence-specific recognition of two 5'-UGUA-3' elements within the
CC pre-mRNA (By similarity). Plays a role in somatic cell fate transitions
CC and pluripotency by regulating widespread changes in gene expression
CC through an APA-dependent function(PubMed:29249356). Binds to chromatin
CC (PubMed:18032416). Binds to, but does not hydrolyze mono- and di-
CC adenosine nucleotides (By similarity). {ECO:0000250|UniProtKB:O43809,
CC ECO:0000269|PubMed:18032416, ECO:0000269|PubMed:29249356}.
CC -!- SUBUNIT: Homodimer (via N- and C-terminus); binds RNA as homodimer.
CC Component of the cleavage factor Im (CFIm) complex which is a
CC heterotetramer composed of two subunits of NUDT21/CPSF5 and two
CC subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7. The
CC cleavage factor Im (CFIm) complex associates with the CPSF and CSTF
CC complexes to promote the assembly of the core mRNA 3'-processing
CC machinery. Interacts with CPSF6 (via the RRM domain); this interaction
CC is direct and enhances binding to RNA. Interacts with CPSF7. Interacts
CC with FIP1L1; this interaction occurs in a RNA sequence-specific manner.
CC Interacts with PABPN1 (By similarity). Interacts (via N-terminus) with
CC PAPOLA (via C-terminus); this interaction is direct and diminished by
CC acetylation (PubMed:11716503). Interacts with SNRNP70 (By similarity).
CC Interacts with VIRMA (By similarity). {ECO:0000250|UniProtKB:O43809,
CC ECO:0000269|PubMed:11716503}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18032416}. Cytoplasm
CC {ECO:0000250|UniProtKB:O43809}. Note=Shuttles between the nucleus and
CC the cytoplasm in a transcription- and XPO1/CRM1-independent manner,
CC most probably in complex with the cleavage factor Im complex (CFIm). In
CC punctate subnuclear structures localized adjacent to nuclear speckles,
CC called paraspeckles. {ECO:0000250|UniProtKB:O43809}.
CC -!- TISSUE SPECIFICITY: Expressed in testis (PubMed:18032416). Expressed in
CC male germ cells (at protein level) (PubMed:18032416).
CC {ECO:0000269|PubMed:18032416}.
CC -!- INDUCTION: Up-regulated during spermatogenesis (PubMed:18032416).
CC {ECO:0000269|PubMed:18032416}.
CC -!- PTM: Acetylated mainly by p300/CBP, recruited to the complex by CPSF6.
CC Acetylation decreases interaction with PAPAO. Deacetylated by the class
CC I/II HDACs, HDAC1, HDAC3 and HDAC10, and by the class III HDACs, SIRT1
CC and SIRT2. {ECO:0000250|UniProtKB:O43809}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. CPSF5 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Lacks the conserved metal-binding residues in the NUDIX motif
CC and is not expected to have hydrolase activity. {ECO:0000305}.
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DR EMBL; AK011688; BAB27778.1; -; mRNA.
DR EMBL; AK019433; BAB31718.1; -; mRNA.
DR EMBL; AK146419; BAE27154.1; -; mRNA.
DR EMBL; AK147061; BAE27645.1; -; mRNA.
DR EMBL; AK160147; BAE35655.1; -; mRNA.
DR EMBL; BC008270; AAH08270.1; -; mRNA.
DR EMBL; BC090834; AAH90834.1; -; mRNA.
DR CCDS; CCDS40433.1; -.
DR RefSeq; NP_080899.1; NM_026623.3.
DR AlphaFoldDB; Q9CQF3; -.
DR SMR; Q9CQF3; -.
DR BioGRID; 212736; 60.
DR IntAct; Q9CQF3; 2.
DR MINT; Q9CQF3; -.
DR STRING; 10090.ENSMUSP00000034204; -.
DR iPTMnet; Q9CQF3; -.
DR PhosphoSitePlus; Q9CQF3; -.
DR EPD; Q9CQF3; -.
DR MaxQB; Q9CQF3; -.
DR PaxDb; 10090-ENSMUSP00000034204; -.
DR PeptideAtlas; Q9CQF3; -.
DR ProteomicsDB; 284003; -.
DR Pumba; Q9CQF3; -.
DR TopDownProteomics; Q9CQF3; -.
DR Antibodypedia; 14781; 271 antibodies from 28 providers.
DR DNASU; 68219; -.
DR Ensembl; ENSMUST00000034204.11; ENSMUSP00000034204.10; ENSMUSG00000031754.11.
DR GeneID; 68219; -.
DR KEGG; mmu:68219; -.
DR UCSC; uc009mvo.1; mouse.
DR AGR; MGI:1915469; -.
DR CTD; 11051; -.
DR MGI; MGI:1915469; Nudt21.
DR VEuPathDB; HostDB:ENSMUSG00000031754; -.
DR eggNOG; KOG1689; Eukaryota.
DR GeneTree; ENSGT00390000015814; -.
DR HOGENOM; CLU_068704_2_1_1; -.
DR InParanoid; Q9CQF3; -.
DR OMA; NDEWEIG; -.
DR OrthoDB; 142507at2759; -.
DR PhylomeDB; Q9CQF3; -.
DR TreeFam; TF106356; -.
DR Reactome; R-MMU-72187; mRNA 3'-end processing.
DR Reactome; R-MMU-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR Reactome; R-MMU-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-MMU-77595; Processing of Intronless Pre-mRNAs.
DR BioGRID-ORCS; 68219; 28 hits in 75 CRISPR screens.
DR ChiTaRS; Nudt21; mouse.
DR PRO; PR:Q9CQF3; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9CQF3; Protein.
DR Bgee; ENSMUSG00000031754; Expressed in superior cervical ganglion and 256 other cell types or tissues.
DR ExpressionAtlas; Q9CQF3; baseline and differential.
DR Genevisible; Q9CQF3; MM.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; ISO:MGI.
DR GO; GO:0005849; C:mRNA cleavage factor complex; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042382; C:paraspeckles; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:1990120; P:messenger ribonucleoprotein complex assembly; ISS:UniProtKB.
DR GO; GO:0031124; P:mRNA 3'-end processing; ISS:UniProtKB.
DR GO; GO:0110104; P:mRNA alternative polyadenylation; ISS:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; IEA:InterPro.
DR GO; GO:0006397; P:mRNA processing; ISS:UniProtKB.
DR GO; GO:2000975; P:positive regulation of pro-B cell differentiation; IMP:UniProtKB.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; ISO:MGI.
DR Gene3D; 3.90.79.10; Nucleoside Triphosphate Pyrophosphohydrolase; 1.
DR InterPro; IPR016706; Cleav_polyA_spec_factor_su5.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR PANTHER; PTHR13047:SF0; CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR SUBUNIT 5; 1.
DR PANTHER; PTHR13047; PRE-MRNA CLEAVAGE FACTOR IM, 25KD SUBUNIT; 1.
DR Pfam; PF13869; NUDIX_2; 1.
DR PIRSF; PIRSF017888; CPSF-25; 1.
DR SUPFAM; SSF55811; Nudix; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Differentiation; Methylation; mRNA processing;
KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT CHAIN 2..227
FT /note="Cleavage and polyadenylation specificity factor
FT subunit 5"
FT /id="PRO_0000057151"
FT DOMAIN 76..201
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 2..147
FT /note="Necessary for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT REGION 81..160
FT /note="Necessary for interactions with PAPOLA and PABPN1"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT REGION 102..104
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT MOTIF 109..130
FT /note="Nudix box"
FT SITE 55
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT SITE 63
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT MOD_RES 15
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 23
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 29
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT MOD_RES 40
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43809"
FT CONFLICT 111
FT /note="L -> F (in Ref. 1; BAE27154)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 227 AA; 26240 MW; 93AEF53557811DC5 CRC64;
MSVVPPNRSQ TGWPRGVNQF GNKYIQQTKP LTLERTINLY PLTNYTFGTK EPLYEKDSSV
AARFQRMREE FDKIGMRRTV EGVLIVHEHR LPHVLLLQLG TTFFKLPGGE LNPGEDEVEG
LKRLMTEILG RQDGVLQDWV IDDCIGNWWR PNFEPPQYPY IPAHITKPKE HKKLFLVQLQ
EKALFAVPKN YKLVAAPLFE LYDNAPGYGP IISSLPQLLS RFNFIYN
//
