CPSF5_HUMAN
ID CPSF5_HUMAN Reviewed; 227 AA.
AC O43809; Q6IB85; Q6NE84;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Cleavage and polyadenylation specificity factor subunit 5 {ECO:0000303|PubMed:23187700};
DE AltName: Full=Cleavage and polyadenylation specificity factor 25 kDa subunit;
DE Short=CPSF 25 kDa subunit;
DE AltName: Full=Cleavage factor Im complex 25 kDa subunit {ECO:0000303|PubMed:9659921};
DE Short=CFIm25 {ECO:0000303|PubMed:9659921};
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 21;
DE Short=Nudix motif 21;
DE AltName: Full=Nudix hydrolase 21 {ECO:0000305};
DE AltName: Full=Pre-mRNA cleavage factor Im 68 kDa subunit;
GN Name=NUDT21 {ECO:0000312|HGNC:HGNC:13870};
GN Synonyms=CFIM25 {ECO:0000303|PubMed:9659921}, CPSF25,
GN CPSF5 {ECO:0000303|PubMed:23187700};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-73 AND 183-189,
RP FUNCTION, IDENTIFICATION IN THE CLEAVAGE FACTOR IM COMPLEX, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=9659921; DOI=10.1016/s1097-2765(00)80025-8;
RA Rueegsegger U., Blank D., Keller W.;
RT "Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins
RT and can be reconstituted in vitro from recombinant subunits.";
RL Mol. Cell 1:243-253(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [6]
RP PROTEIN SEQUENCE OF 2-15; 24-50 AND 79-131, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP FUNCTION, IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, AND RNA-BINDING.
RX PubMed=8626397; DOI=10.1074/jbc.271.11.6107;
RA Rueegsegger U., Beyer K., Keller W.;
RT "Purification and characterization of human cleavage factor Im involved in
RT the 3' end processing of messenger RNA precursors.";
RL J. Biol. Chem. 271:6107-6113(1996).
RN [8]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=14690600; DOI=10.1016/s1097-2765(03)00453-2;
RA Brown K.M., Gilmartin G.M.;
RT "A mechanism for the regulation of pre-mRNA 3' processing by human cleavage
RT factor Im.";
RL Mol. Cell 12:1467-1476(2003).
RN [9]
RP IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH CPSF6 AND
RP SNRNP70, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14561889; DOI=10.1261/rna.5104603;
RA Awasthi S., Alwine J.C.;
RT "Association of polyadenylation cleavage factor I with U1 snRNP.";
RL RNA 9:1400-1409(2003).
RN [10]
RP IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH CPSF6;
RP PAPOLA AND PABPN1, RNA-BINDING, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=15169763; DOI=10.1074/jbc.m403927200;
RA Dettwiler S., Aringhieri C., Cardinale S., Keller W., Barabino S.M.;
RT "Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im
RT mediate RNA binding, protein-protein interactions, and subcellular
RT localization.";
RL J. Biol. Chem. 279:35788-35797(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH FIP1L1.
RX PubMed=15937220; DOI=10.1101/gad.1298605;
RA Venkataraman K., Brown K.M., Gilmartin G.M.;
RT "Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for
RT vertebrate poly(A) site recognition.";
RL Genes Dev. 19:1315-1327(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-40, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP FUNCTION.
RX PubMed=17024186; DOI=10.1038/sj.emboj.7601331;
RA Millevoi S., Loulergue C., Dettwiler S., Karaa S.Z., Keller W.,
RA Antoniou M., Vagner S.;
RT "An interaction between U2AF 65 and CF I(m) links the splicing and 3' end
RT processing machineries.";
RL EMBO J. 25:4854-4864(2006).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17098938; DOI=10.1093/nar/gkl794;
RA Kubo T., Wada T., Yamaguchi Y., Shimizu A., Handa H.;
RT "Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters
RT alternative polyadenylation within 3'-UTRs.";
RL Nucleic Acids Res. 34:6264-6271(2006).
RN [15]
RP ACETYLATION AT LYS-23, INTERACTION WITH PAPOLA AND CPSF6, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-23 AND LYS-29.
RX PubMed=17172643; DOI=10.1074/jbc.m609745200;
RA Shimazu T., Horinouchi S., Yoshida M.;
RT "Multiple histone deacetylases and the CREB-binding protein regulate pre-
RT mRNA 3'-end processing.";
RL J. Biol. Chem. 282:4470-4478(2007).
RN [16]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CPSF6.
RX PubMed=19864460; DOI=10.1091/mbc.e09-05-0389;
RA Ruepp M.D., Aringhieri C., Vivarelli S., Cardinale S., Paro S.,
RA Schuemperli D., Barabino S.M.;
RT "Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA
RT export.";
RL Mol. Biol. Cell 20:5211-5223(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-23; LYS-29 AND LYS-56, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [18]
RP FUNCTION, IDENTIFICATION IN THE CLEAVAGE FACTOR IM COMPLEX, SUBUNIT,
RP SUBSTRATE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=20695905; DOI=10.1111/j.1365-2443.2010.01436.x;
RA Kim S., Yamamoto J., Chen Y., Aida M., Wada T., Handa H., Yamaguchi Y.;
RT "Evidence that cleavage factor Im is a heterotetrameric protein complex
RT controlling alternative polyadenylation.";
RL Genes Cells 15:1003-1013(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP RNA-BINDING.
RX PubMed=22813749; DOI=10.1016/j.celrep.2012.05.003;
RA Martin G., Gruber A.R., Keller W., Zavolan M.;
RT "Genome-wide analysis of pre-mRNA 3' end processing reveals a decisive role
RT of human cleavage factor I in the regulation of 3' UTR length.";
RL Cell Rep. 1:753-763(2012).
RN [21]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23187700; DOI=10.4161/rna.22570;
RA Gruber A.R., Martin G., Keller W., Zavolan M.;
RT "Cleavage factor Im is a key regulator of 3' UTR length.";
RL RNA Biol. 9:1405-1412(2012).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-15, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
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 [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [25]
RP INTERACTION WITH VIRMA.
RX PubMed=29507755; DOI=10.1038/s41421-018-0019-0;
RA Yue Y., Liu J., Cui X., Cao J., Luo G., Zhang Z., Cheng T., Gao M., Shu X.,
RA Ma H., Wang F., Wang X., Shen B., Wang Y., Feng X., He C., Liu J.;
RT "VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop
RT codon and associates with alternative polyadenylation.";
RL Cell Discov. 4:10-10(2018).
RN [26]
RP FUNCTION, INTERACTION WITH CPSF6 AND CPSF7, IDENTIFICATION IN THE MRNA
RP 3'-PROCESSING COMPLEX, AND MUTAGENESIS OF LEU-218.
RX PubMed=29276085; DOI=10.1016/j.molcel.2017.11.031;
RA Zhu Y., Wang X., Forouzmand E., Jeong J., Qiao F., Sowd G.A.,
RA Engelman A.N., Xie X., Hertel K.J., Shi Y.;
RT "Molecular mechanisms for CFIm-mediated regulation of mRNA alternative
RT polyadenylation.";
RL Mol. Cell 69:62-74(2018).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF APO FORM AND IN COMPLEX WITH BETA
RP DIADENOSINE TETRAPHOSPHATE, LACK OF METAL-BINDING, AND HOMODIMERIZATION.
RX PubMed=18445629; DOI=10.1093/nar/gkn079;
RA Coseno M., Martin G., Berger C., Gilmartin G., Keller W., Doublie S.;
RT "Crystal structure of the 25 kDa subunit of human cleavage factor Im.";
RL Nucleic Acids Res. 36:3474-3483(2008).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF APO FORM AND IN COMPLEX WITH
RP SULFATE.
RX PubMed=18767156; DOI=10.1002/prot.22198;
RA Tresaugues L., Stenmark P., Schaeler H., Flodin S., Welin M., Nyman T.,
RA Hammarstroem M., Moche M., Graeslund S., Nordlund P.;
RT "The crystal structure of human cleavage and polyadenylation specific
RT factor-5 reveals a dimeric Nudix protein with a conserved catalytic site.";
RL Proteins 73:1047-1052(2008).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) IN COMPLEXES WITH RNA UGUAAA AND
RP UUGUAU, FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLU-55; ARG-63; GLU-81 AND
RP PHE-103.
RX PubMed=20479262; DOI=10.1073/pnas.1000848107;
RA Yang Q., Gilmartin G.M., Doublie S.;
RT "Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and
RT implications for a regulatory role in mRNA 3' processing.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10062-10067(2010).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 21-227 IN COMPLEX WITH CPSF7, AND
RP SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex between the 25 kDA subunit and the 59 kDA
RT subunit (RRM domain) of human cleavage factor Im.";
RL Submitted (JUL-2010) to the PDB data bank.
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 21-227 IN COMPLEX WITH CPSF6 AND
RP RNA, FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLU-55; ARG-63; PHE-103; TYR-158
RP AND TYR-160.
RX PubMed=21295486; DOI=10.1016/j.str.2010.12.021;
RA Yang Q., Coseno M., Gilmartin G.M., Doublie S.;
RT "Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex
RT provides an insight into poly(A) site recognition and RNA looping.";
RL Structure 19:368-377(2011).
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 (PubMed:9659921, PubMed:8626397, PubMed:14690600,
CC PubMed:15937220, PubMed:17024186, PubMed:17098938, PubMed:29276085).
CC CFIm contributes to the recruitment of multiprotein complexes on
CC specific sequences on the pre-mRNA 3'-end, so called cleavage and
CC polyadenylation signals (pA signals) (PubMed:9659921, PubMed:8626397,
CC PubMed:14690600, PubMed:17024186). Most pre-mRNAs contain multiple pA
CC signals, resulting in alternative cleavage and polyadenylation (APA)
CC producing mRNAs with variable 3'-end formation (PubMed:17098938,
CC PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key
CC regulator of cleavage and polyadenylation site choice during APA
CC through its binding to 5'-UGUA-3' elements localized in the 3'-
CC untranslated region (UTR) for a huge number of pre-mRNAs
CC (PubMed:17098938, PubMed:20695905, PubMed:29276085). NUDT21/CPSF5
CC activates indirectly the mRNA 3'-processing machinery by recruiting
CC CPSF6 and/or CPSF7 (PubMed:29276085). Binds to 5'-UGUA-3' elements
CC localized upstream of pA signals that act as enhancers of pre-mRNA 3'-
CC end processing (PubMed:8626397, PubMed:14690600, PubMed:15169763,
CC PubMed:17024186, PubMed:22813749, PubMed:20479262). The homodimer
CC mediates simultaneous sequence-specific recognition of two 5'-UGUA-3'
CC elements within the pre-mRNA (PubMed:20479262, PubMed:21295486). Plays
CC a role in somatic cell fate transitions and pluripotency by regulating
CC widespread changes in gene expression through an APA-dependent function
CC (By similarity). Binds to chromatin (By similarity). Binds to, but does
CC not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629).
CC {ECO:0000250|UniProtKB:Q9CQF3, ECO:0000269|PubMed:14690600,
CC ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:15937220,
CC ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:17098938,
CC ECO:0000269|PubMed:18445629, ECO:0000269|PubMed:20479262,
CC ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:21295486,
CC ECO:0000269|PubMed:22813749, ECO:0000269|PubMed:23187700,
CC ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397,
CC ECO:0000269|PubMed:9659921}.
CC -!- SUBUNIT: Homodimer (via N- and C-terminus); binds RNA as homodimer
CC (PubMed:20695905, PubMed:18445629, PubMed:20479262). Component of the
CC cleavage factor Im (CFIm) complex which is a heterotetramer composed of
CC two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or a
CC heterodimer of CPSF6 and CPSF7 (PubMed:9659921, PubMed:8626397,
CC PubMed:14561889, PubMed:20695905, PubMed:23187700, PubMed:21295486).
CC The 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 (PubMed:29276085). Interacts with CPSF6 (via the RRM domain);
CC this interaction is direct and enhances binding to RNA
CC (PubMed:14561889, PubMed:15169763, PubMed:17172643, PubMed:19864460,
CC PubMed:29276085). Interacts with CPSF7 (PubMed:29276085, Ref.30).
CC Interacts with FIP1L1; this interaction occurs in a RNA sequence-
CC specific manner (PubMed:15937220). Interacts with PABPN1
CC (PubMed:15169763). Interacts (via N-terminus) with PAPOLA (via C-
CC terminus); this interaction is direct and diminished by acetylation
CC (PubMed:15169763, PubMed:17172643). Interacts with SNRNP70
CC (PubMed:14561889). Interacts with VIRMA (PubMed:29507755).
CC {ECO:0000269|PubMed:14561889, ECO:0000269|PubMed:15169763,
CC ECO:0000269|PubMed:15937220, ECO:0000269|PubMed:17172643,
CC ECO:0000269|PubMed:18445629, ECO:0000269|PubMed:19864460,
CC ECO:0000269|PubMed:20479262, ECO:0000269|PubMed:20695905,
CC ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:23187700,
CC ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:29507755,
CC ECO:0000269|PubMed:8626397, ECO:0000269|PubMed:9659921,
CC ECO:0000269|Ref.30}.
CC -!- INTERACTION:
CC O43809; P54253: ATXN1; NbExp=8; IntAct=EBI-355720, EBI-930964;
CC O43809; Q86X55: CARM1; NbExp=2; IntAct=EBI-355720, EBI-2339854;
CC O43809; Q16630: CPSF6; NbExp=5; IntAct=EBI-355720, EBI-358410;
CC O43809; Q16630-1: CPSF6; NbExp=4; IntAct=EBI-355720, EBI-1019636;
CC O43809; Q16630-2: CPSF6; NbExp=7; IntAct=EBI-355720, EBI-11088043;
CC O43809; Q8N684: CPSF7; NbExp=5; IntAct=EBI-355720, EBI-746909;
CC O43809; Q8N684-3: CPSF7; NbExp=3; IntAct=EBI-355720, EBI-11523759;
CC O43809; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-355720, EBI-6658203;
CC O43809; P14136: GFAP; NbExp=3; IntAct=EBI-355720, EBI-744302;
CC O43809; Q08379: GOLGA2; NbExp=3; IntAct=EBI-355720, EBI-618309;
CC O43809; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-355720, EBI-11522367;
CC O43809; O95678: KRT75; NbExp=3; IntAct=EBI-355720, EBI-2949715;
CC O43809; P60660: MYL6; NbExp=5; IntAct=EBI-355720, EBI-300817;
CC O43809; Q96HA8: NTAQ1; NbExp=5; IntAct=EBI-355720, EBI-741158;
CC O43809; O43809: NUDT21; NbExp=6; IntAct=EBI-355720, EBI-355720;
CC O43809; Q8WXF1-2: PSPC1; NbExp=3; IntAct=EBI-355720, EBI-12135327;
CC O43809; Q96BU1: S100PBP; NbExp=3; IntAct=EBI-355720, EBI-18959794;
CC O43809; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-355720, EBI-11959123;
CC O43809; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-355720, EBI-11139477;
CC O43809; P36406: TRIM23; NbExp=3; IntAct=EBI-355720, EBI-740098;
CC O43809; P14373: TRIM27; NbExp=6; IntAct=EBI-355720, EBI-719493;
CC O43809; Q8N720: ZNF655; NbExp=3; IntAct=EBI-355720, EBI-625509;
CC O43809; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-355720, EBI-527853;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15169763,
CC ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905,
CC ECO:0000269|PubMed:9659921}. Cytoplasm {ECO:0000269|PubMed:19864460}.
CC Note=Shuttles between the nucleus and the cytoplasm in a
CC transcription- and XPO1/CRM1-independent manner, most probably in
CC complex with the cleavage factor Im complex (CFIm) (PubMed:19864460).
CC In punctate subnuclear structures localized adjacent to nuclear
CC speckles, called paraspeckles (PubMed:15169763).
CC {ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:19864460}.
CC -!- TISSUE SPECIFICITY: Expressed in the heart, brain, placenta, lung,
CC liver, skeletal muscle, kidney and pancreas.
CC {ECO:0000269|PubMed:17098938}.
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:0000269|PubMed:17172643}.
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 does not have hydrolase activity. {ECO:0000305}.
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DR EMBL; AJ001810; CAA05026.1; -; mRNA.
DR EMBL; CR456919; CAG33200.1; -; mRNA.
DR EMBL; BX537360; CAD97606.1; -; mRNA.
DR EMBL; AC092140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001403; AAH01403.1; -; mRNA.
DR CCDS; CCDS10760.1; -.
DR RefSeq; NP_008937.1; NM_007006.2.
DR PDB; 2CL3; X-ray; 1.90 A; A=21-227.
DR PDB; 2J8Q; X-ray; 2.30 A; A/B=24-227.
DR PDB; 3BAP; X-ray; 1.85 A; A=1-227.
DR PDB; 3BHO; X-ray; 1.80 A; A=20-227.
DR PDB; 3MDG; X-ray; 2.22 A; A/B=1-227.
DR PDB; 3MDI; X-ray; 2.07 A; A/B=1-227.
DR PDB; 3N9U; X-ray; 1.92 A; A/B=21-227.
DR PDB; 3P5T; X-ray; 2.70 A; A/B/C/D/E/F=34-227.
DR PDB; 3P6Y; X-ray; 2.90 A; A/B/E/F/I/J/M/N=34-227.
DR PDB; 3Q2S; X-ray; 2.90 A; A/B=21-227.
DR PDB; 3Q2T; X-ray; 3.06 A; A/B=21-227.
DR PDB; 5R4P; X-ray; 1.78 A; A/B=33-227.
DR PDB; 5R4Q; X-ray; 1.49 A; A/B=33-227.
DR PDB; 5R4R; X-ray; 1.50 A; A/B=33-227.
DR PDB; 5R4S; X-ray; 1.61 A; A/B=33-227.
DR PDB; 5R4T; X-ray; 1.68 A; A/B=33-227.
DR PDB; 5R4U; X-ray; 1.92 A; A/B=33-227.
DR PDB; 5R64; X-ray; 1.84 A; A/B=33-227.
DR PDB; 5R65; X-ray; 2.28 A; A/B=33-227.
DR PDB; 5R66; X-ray; 2.02 A; A/B=33-227.
DR PDB; 5R67; X-ray; 1.52 A; A/B=33-227.
DR PDBsum; 2CL3; -.
DR PDBsum; 2J8Q; -.
DR PDBsum; 3BAP; -.
DR PDBsum; 3BHO; -.
DR PDBsum; 3MDG; -.
DR PDBsum; 3MDI; -.
DR PDBsum; 3N9U; -.
DR PDBsum; 3P5T; -.
DR PDBsum; 3P6Y; -.
DR PDBsum; 3Q2S; -.
DR PDBsum; 3Q2T; -.
DR PDBsum; 5R4P; -.
DR PDBsum; 5R4Q; -.
DR PDBsum; 5R4R; -.
DR PDBsum; 5R4S; -.
DR PDBsum; 5R4T; -.
DR PDBsum; 5R4U; -.
DR PDBsum; 5R64; -.
DR PDBsum; 5R65; -.
DR PDBsum; 5R66; -.
DR PDBsum; 5R67; -.
DR AlphaFoldDB; O43809; -.
DR SMR; O43809; -.
DR BioGRID; 116237; 312.
DR ComplexPortal; CPX-941; mRNA cleavage factor I(m) complex, CPSF6 variant.
DR ComplexPortal; CPX-951; mRNA cleavage factor I(m) complex, CPSF7 variant.
DR CORUM; O43809; -.
DR DIP; DIP-42502N; -.
DR IntAct; O43809; 114.
DR MINT; O43809; -.
DR STRING; 9606.ENSP00000300291; -.
DR GlyGen; O43809; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43809; -.
DR MetOSite; O43809; -.
DR PhosphoSitePlus; O43809; -.
DR SwissPalm; O43809; -.
DR BioMuta; NUDT21; -.
DR UCD-2DPAGE; O43809; -.
DR EPD; O43809; -.
DR jPOST; O43809; -.
DR MassIVE; O43809; -.
DR MaxQB; O43809; -.
DR PaxDb; O43809; -.
DR PeptideAtlas; O43809; -.
DR PRIDE; O43809; -.
DR ProteomicsDB; 49176; -.
DR TopDownProteomics; O43809; -.
DR Antibodypedia; 14781; 241 antibodies from 28 providers.
DR DNASU; 11051; -.
DR Ensembl; ENST00000300291.10; ENSP00000300291.5; ENSG00000167005.14.
DR GeneID; 11051; -.
DR KEGG; hsa:11051; -.
DR MANE-Select; ENST00000300291.10; ENSP00000300291.5; NM_007006.3; NP_008937.1.
DR UCSC; uc002eja.4; human.
DR CTD; 11051; -.
DR DisGeNET; 11051; -.
DR GeneCards; NUDT21; -.
DR HGNC; HGNC:13870; NUDT21.
DR HPA; ENSG00000167005; Low tissue specificity.
DR MIM; 604978; gene.
DR neXtProt; NX_O43809; -.
DR OpenTargets; ENSG00000167005; -.
DR PharmGKB; PA26845; -.
DR VEuPathDB; HostDB:ENSG00000167005; -.
DR eggNOG; KOG1689; Eukaryota.
DR GeneTree; ENSGT00390000015814; -.
DR HOGENOM; CLU_068704_2_1_1; -.
DR InParanoid; O43809; -.
DR OMA; EHYEQYG; -.
DR OrthoDB; 1194206at2759; -.
DR PhylomeDB; O43809; -.
DR TreeFam; TF106356; -.
DR PathwayCommons; O43809; -.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-HSA-77595; Processing of Intronless Pre-mRNAs.
DR SignaLink; O43809; -.
DR SIGNOR; O43809; -.
DR BioGRID-ORCS; 11051; 817 hits in 1077 CRISPR screens.
DR ChiTaRS; NUDT21; human.
DR EvolutionaryTrace; O43809; -.
DR GeneWiki; NUDT21; -.
DR GenomeRNAi; 11051; -.
DR Pharos; O43809; Tbio.
DR PRO; PR:O43809; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O43809; protein.
DR Bgee; ENSG00000167005; Expressed in ganglionic eminence and 205 other tissues.
DR ExpressionAtlas; O43809; baseline and differential.
DR Genevisible; O43809; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005813; C:centrosome; IDA:LIFEdb.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IDA:UniProtKB.
DR GO; GO:0005849; C:mRNA cleavage factor complex; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042382; C:paraspeckles; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:1990120; P:messenger ribonucleoprotein complex assembly; IDA:UniProtKB.
DR GO; GO:0031124; P:mRNA 3'-end processing; IDA:ComplexPortal.
DR GO; GO:0110104; P:mRNA alternative polyadenylation; IMP:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; IEA:InterPro.
DR GO; GO:0006397; P:mRNA processing; IDA:UniProtKB.
DR GO; GO:0031439; P:positive regulation of mRNA cleavage; IDA:UniProtKB.
DR GO; GO:1900365; P:positive regulation of mRNA polyadenylation; IDA:UniProtKB.
DR GO; GO:2000975; P:positive regulation of pro-B cell differentiation; ISS:UniProtKB.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0098789; P:pre-mRNA cleavage required for polyadenylation; IDA:ComplexPortal.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
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; PTHR13047; 1.
DR Pfam; PF13869; NUDIX_2; 1.
DR PIRSF; PIRSF017888; CPSF-25; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Differentiation;
KW Direct protein sequencing; Methylation; mRNA processing; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6"
FT CHAIN 2..227
FT /note="Cleavage and polyadenylation specificity factor
FT subunit 5"
FT /id="PRO_0000057150"
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:0000269|PubMed:15169763"
FT REGION 81..160
FT /note="Necessary for interactions with PAPOLA and PABPN1"
FT /evidence="ECO:0000269|PubMed:15169763"
FT REGION 102..104
FT /note="Interaction with RNA"
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000269|PubMed:21295486, ECO:0000312|PDB:3MDG,
FT ECO:0000312|PDB:3MDI, ECO:0000312|PDB:3Q2T"
FT MOTIF 109..130
FT /note="Nudix box"
FT SITE 55
FT /note="Interaction with RNA"
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000312|PDB:3MDG, ECO:0000312|PDB:3MDI"
FT SITE 63
FT /note="Interaction with RNA"
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000312|PDB:3MDG, ECO:0000312|PDB:3MDI"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.6"
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:0000269|PubMed:17172643,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 29
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 40
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MUTAGEN 23
FT /note="K->R: Abolishes acetylation."
FT /evidence="ECO:0000269|PubMed:17172643"
FT MUTAGEN 29
FT /note="K->R: No effect on acetylation."
FT /evidence="ECO:0000269|PubMed:17172643"
FT MUTAGEN 55
FT /note="E->A: Reduces affinity for UGUA RNA by 88%."
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000269|PubMed:21295486"
FT MUTAGEN 63
FT /note="R->S: Reduces affinity for UGUA RNA by 99%."
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000269|PubMed:21295486"
FT MUTAGEN 81
FT /note="E->A: Reduces affinity for UGUA RNA by 12%."
FT /evidence="ECO:0000269|PubMed:20479262"
FT MUTAGEN 103
FT /note="F->A: Reduces affinity for UGUA RNA by 99%."
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000269|PubMed:21295486"
FT MUTAGEN 103
FT /note="F->W: Reduces affinity for UGUA RNA by over 90%."
FT /evidence="ECO:0000269|PubMed:20479262,
FT ECO:0000269|PubMed:21295486"
FT MUTAGEN 154
FT /note="E->A: Reduces affinity for UGUA RNA by 50%."
FT MUTAGEN 158
FT /note="Y->A: Abolishes interaction with CPSF6; when
FT associated with A-160."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 160
FT /note="Y->A: Abolishes interaction with CPSF6; when
FT associated with A-158."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 218
FT /note="L->R: Reduces interactions with CPSF6 and CPSF7 and
FT decreases mRNA 3'-processing activity."
FT /evidence="ECO:0000269|PubMed:29276085"
FT CONFLICT 57
FT /note="D -> G (in Ref. 2; CAG33200)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="N -> D (in Ref. 3; CAD97606)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="L -> P (in Ref. 3; CAD97606)"
FT /evidence="ECO:0000305"
FT TURN 31..33
FT /evidence="ECO:0007829|PDB:3BHO"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:5R4Q"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:5R4Q"
FT HELIX 60..74
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 76..88
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 91..99
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:3BAP"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:3BHO"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:5R4Q"
FT HELIX 117..129
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:3N9U"
FT STRAND 140..150
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 169..178
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:5R4Q"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:5R4Q"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:5R4Q"
FT HELIX 215..219
FT /evidence="ECO:0007829|PDB:5R4Q"
FT STRAND 222..226
FT /evidence="ECO:0007829|PDB:5R4Q"
SQ SEQUENCE 227 AA; 26227 MW; D204243E57F1CCC5 CRC64;
MSVVPPNRSQ TGWPRGVTQF GNKYIQQTKP LTLERTINLY PLTNYTFGTK EPLYEKDSSV
AARFQRMREE FDKIGMRRTV EGVLIVHEHR LPHVLLLQLG TTFFKLPGGE LNPGEDEVEG
LKRLMTEILG RQDGVLQDWV IDDCIGNWWR PNFEPPQYPY IPAHITKPKE HKKLFLVQLQ
EKALFAVPKN YKLVAAPLFE LYDNAPGYGP IISSLPQLLS RFNFIYN
